Effect of colchicine on cancer risk in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases

Effect of colchicine on cancer risk in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of colchicine on cancer risk in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases Jun-Jun Yeh, Pei-Xuan Liw, Yi-Sin Wong, Husan-Min Kao, Chia-Hsun Lee, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3789273/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background To determine the effect of colchicine on cancer risk in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases (MD). Methods We retrospectively enrolled patients with the MD divided them into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for tobacco use, anti-inflammatory drugs and immunosuppressant drugs. Results Comparing the colchicine nonusers, only the colchicine users were associated with the lower incidence of the colorectal cancer ( (aHRs) (95% CI), 0.52 (0.49, 0.89)). Notably, the frequency of the medical services may inflate the aHR of brain tumor ((aHRs (95% CI), 8.42 (1.32, 53.9)). However, the aged 20 days use with the lower aHR for colorectal cancer. Conclusion This study implied colchicine with an auxiliary role for protecting the colorectal cancer formation in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases. colchicine cancer risk musculoskeletal system connective tissue rheumatism-related diseases Figures Figure 1 Introduction The pyrin domain–containing protein 3 (or NOD-like receptor protein 3 [NLRP3]) inflammasome and NLRP3 inflammasome related cytokines -interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6) have been associated with colorectal cancer formation [ 1 ]. Notably, these markers would increase, especially in patients with the gout, diabetes, obesity and cancer [ 1 ]. The role of the NLRP3 inflammasome varies according to sex, age, and tumor type. For example, estrogen enhances the expression of NLRP3 inflammasome, whereas testosterone inhibits its expression. The estrogen acts through estrogen receptor β (ERβ) to enhance the activation of NLPR3 inflammasome and promote the progression of endometrial cancer [ 2 ]. Similarly, NLRP3 inflammasome protects against the bowel inflammation associated-tumor formation in chronic stages but promotes colon cancer in the early stage of the colitis [ 1 , 3 , 4 ]. In contrast, Zaki et al study the consequence of a decrease in IL-18 in mice lacking components of the NLRP3 inflammasome, resulting in higher mortality rates. Thus, the NLRP3 inflammasome may be critically involved in the maintenance of intestinal homeostasis and protection against colitis [ 4 ]. Hence, NLRP3 inflammasome exhibits contrasting roles in cancer development [ 1 , 5 ]. Colchicine is an anti-inflammatory drug, it have been used in the gout and nongout conditions such as arthritis- c rystal arthropathies, systemic inflammatory diseases such as sarcoidosis, Behcet's syndrome, autoimmune disease, chronic idiopathic or spontaneous urticarial skin diseases, allergic purpura, psoriasis, collagen vascular diseases, and cardiovascular -related diseases [ 3 , 6 – 8 ]. In addition, colchicine exerts its unique effects by the retardation of new tubulin formation, dissociation of tubulin, thus leading to cancer cell death. In addition, colchicine inhibits angiogenesis and cancer cell migration and metastasis, limits ATP influx into mitochondria, and releases caspases and cytochrome-c, thus leading to apoptosis [ 1 , 9 ]. Colchicine could also inhibit neutrophil function, and attenuate expression of IL-6 and NLRP3 inflammasome. Altogether, colchicine could play an auxiliary role in the prevention of cancer in patients with gout [ 10 ]. The important evidence that links inflammation and cancer is that nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, reduce the risk and mortality from many cancers. In recent study, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout [ 10 ]. The musculoskeletal system and connective tissue and rheumatism-related diseases (MD) such as the gout, autoimmune disease (eg, ulcerative colitis, Crohn’s disease), psoriasis are associated with the risk of cancer. However, rare research has examined the role of colchicine in the evolution of cancer among patients with MD. Thus, in this study, we investigated the effect of colchicine on the development of cancer in patients with MD by using a general population design. Methods Data source We analyzed the Longitudinal Health Insurance Database, a subset of the NHIRD that contains demographic information, inpatient and outpatient records, medications, and treatments of 2 million insured individuals. Study population Excluding criteria including: patients younger than 20 years old, with previous history of cancer ( ICD-9-CM codes 140–239), as well as those with additional indications for colchicine treatment (eg, Bechet’s disease) [ 7 , 11 , 12 ]. Including criteria as below: patients who used colchicine between 2000 and 2012 were defined as colchicine users among patients with MD [ 6 – 8 , 12 , 13 ]. And, these patients had at least two outpatients visits or an inpatient visit. The colchicine users need fulfill criteria as below: 1) In Lin et study, the nude mice experiment showed that colchicine-treated mice after 14 days of treatment had lower increased tumor volume ratios and tumor growth rates than the control. In accordance with this previous study, we set the duration of the colchicine use > 15 days [ 14 ]; 2) Incident use of drugs increases in the months prior to a cancer diagnosis. To avoid reverse causation, 6 months’ lag time would be sufficient for most drug-cancer associations. In this study, to avoid this reverse causation, the lag time would be set as ≧ 12 months from the first prescription of colchicine to any diagnosis of cancer [ 15 , 16 ]. Nonusers defined as those who never used colchicine or prescriptions within 12 months of diagnosis of cancer were not considered as exposed, again to avoid reverse causation [ 16 ]. For those who had more than one prescription of immunosuppressants, a minimum of 7 days between prescriptions was required. Owing to this a time-dependent study, the index date for the colchicine users was the date of the first prescription of colchicine, and a date between 2000 and 2012 was the index date for the non-users. Colchicine users and nonusers were then matched by propensity scores according to age, sex, comorbidities, medications and index date. The International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ) diagnosis codes considered for patients with the MD. (Full names, Supplemental Table 1 ). Licensing Committee (Ethics Statement) The NHIRD encrypts patient personal information to protect privacy and provides researchers with anonymous identification numbers associated with relevant claims information, including sex, date of birth, medical services received, and prescriptions. All methods were carried out in accordance with relevant guidelines and regulations. Therefore, patient consent is not required to access the NHIRD. This study was approved to fulfill the condition for exemption by the Institutional Review Board (IRB) of China Medical University & Hospital Research Ethics Center (CMUH104-REC2-115[CR-7]). The IRB also specifically waived the consent requirement. Data Availability Statement The dataset used in this study is held by the Taiwan Ministry of Health and Welfare (MOHW). The Ministry of Health and Welfare must approve our application to access this data. Any researcher interested in accessing this dataset can submit an application form to the Ministry of Health and Welfare requesting access. Please contact the staff of MOHW (Email: [email protected] ) for further assistance. Taiwan Ministry of Health and Welfare Address: No.488, Sec. 6, Zhongxiao E. Rd., Nangang Dist., Taipei City 115, Taiwan (R.O.C.). Phone: +886-2-8590-6848. All relevant data are within the paper. Main outcome and covariates The primary endpoint of this study was the development of cancer ( ICD-9-CM codes 140–239), as evidenced by a major illness or injury certificate of cancer. The study endpoint was defined as the occurrence of cancer, withdrawal from the insurance program, or December 31, 2013. In addition to age and sex, other potential confounders included comorbidities (Full names, Supplemental Table 1 ). The use of acetylcysteine, smoking cessation–related medication, anti-inflammatory drugs (aspirin, NSAID) and immunosuppressant drugs was evaluated as a confounder also. The severity and duration of MD have impact on the risk of cancer. Owing to the comorbidities and medications were close relation to the MD severity and duration [ 17 ]. Thus, these comorbidities, medications and Charleson Co-morbidity index enter into analysis in this study. Meanwhile, we used alcohol related diseases as a proxy for drinking, chronic obstructive pulmonary disease (COPD) and tobacco use for smoking, gout and hypertension and hyperlipidemia for exercise and life style [ 18 , 19 ]. The Anatomical Therapeutic Chemical code (ATC) of medications were defined as a prescription with one of the following National Health Insurance (NHI) codes: ( Supplemental Table 1). Statistical analysis Categorical variables were expressed as number and percentage, and differences between the two cohorts were examined using the chi-square test. Continuous variables were presented as median and interquartile range, and differences between the two cohorts were assessed using the Mann–Whitney U test. The incidence rate was expressed as per 1,000 person-years. The disease duration might impact on the risk of cancer and should be taken into account. Thus, the Cox proportional hazards (PH) model with time-dependent exposure covariates was used as the main model in the study to analyze the effect of colchicine on cancer. The association between the duration of colchicine use and the development of cancer was analyzed using the general Cox PH model. The Kaplan-Meier method was used to obtain the cumulative curves, and the results were then examined using the log-rank test. SAS statistical software (version 9.1, SAS Institute, Cary, NC) was used to perform the analysis. A p-value less than .05 was set as the significant level. Result A total of 22,464 patients were defined as colchicine users in this study ( Table 1 ). The median age of the colchicine users was higher than that of the colchicine nonusers: 54.3 years versus 53.7 years, respectively. A male preponderance was observed in the colchicine users compared with the colchicine nonusers. As this is a time-dependent study, more patients had developed comorbidities such as alcohol-related diseases, diabetes, hypertension and hyperlipidemia in the colchicine users than in the colchicine nonusers. In addition, the colchicine users included more patients who used acetylcysteine, smoking cessation-related medication, anti-inflammatory drugs such as oral steroids (OSs), non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, and immunosuppressant drugs such as azathioprine, sulfasalazine, cyclophosphamide, methotrexate, hydroxychloroquine, and cyclosporine. After propensity score matching, both cohorts included 16,026 patients each. Both cohorts had a similar distribution of age, sex, comorbidities, and medications. Table 2 illustrates the association of colchicine use with different types of cancer in the colchicine users. Compared with colchicine nonusers, the colorectal cancer and brain tumor in the colchicine users were associated with the different adjusted HRs [aHRs], the aHRs (95 % CI) were 0.52 (0.49, 0.89), and 8.42 (1.32, 53.9)), respectively. The colchicine users were associated with the lower incidence of the colorectal cancer (Figure 1) . Table 3 illustrates the colchcine use with >20 days having the lower aHR for the colorectal cancer. Investigate the impact of the sex and age on the cancers formation The elderly with colchicine use having the null effect for the aHR of colorectal cancer. Regarding the young adult, the aHRs for colorectal cancer were associated with the lower aHRs for the colchicine users. (Table 4) C ovariates in proxies to the NLRP3 expression for the incident cancer. The NLRP3 expression were unavailable in the NHIRD. However, the NLRP3 expression in accordance with the cell type, duration of use, age, sex. Meanwhile, these variables were independent and critical factors of the colchicine on the cancer promotion [14, 20-23]. Moreover, those covariates such as comorbidities (eg, alcohol-related disease, hypertension, diabetes, depression, tobacco use) in proxies to the NLRP3 expression for the incident cancer [21, 24]. Therein, these variants were entered into the analysis [1, 25]. Sensitivity analysis - Propensity score analysis for time-dependent exposure In different cell line and comorbidities The colchicine users have the higher aHR of brain tumor and lower aHR of colorectal cancer. Combination of the NLRP3 dual effect for cancer, colchicine modulates NLRP3 effect for cancer, duration of drug effect and detection bias could play a role for contributing to these results. We did sensitivity analysis for clarifying these points for colorectal cancer. (Table 4, 5) . We displayed these speculations in the Table 5 : 1) the combination the effect of the colchicine, NLRP3, comorbidities and detection bias on the risk of cancer in colorectal cancer with chronic colitis; 2) sex and age for modulation the effect of the colchicine on the risk of colorectal cancer [26, 27]. DISCUSSION The main finding of our study was that colchicine use was associated with a lower risk of the colorectal cancer in patients with the MD. The Kaplan–Meier was used only one variable (event of interest-colchicine use) for estimating the survival curves. Log rank test compares two or more survival curves and does not consider additional independent variables. Similar to multiple regression model, Cox PH model considers additional independent variables (covariates-age, sex, comorbidities) for estimating the differences between the survival curves. To the best of our knowledge, this study is the first study to report an association between colchicine use and incidental cancers in patients with the MD, who were associated with the lower risk of colorectal cancer based on the Cox PH model with time-dependent exposure. Similar to that, the colchicine users were associated with the lower cumulative incidence of the colorectal cancer in analysis of the Kaplan-Meier method. An important confounding factor of this study is the detection bias. Detection bias is hypothesized, in part, because of observed differences between the colchicine users and colchicine nonusers. Detection bias occurs when screening and diagnostic patterns vary in association with potential risk factors. Detection bias could exaggerate or attenuate estimated cancer-colchicine associations and affecting the aHR for cancer. For example, the aged > 65 received the higher frequency of neurodegenerative diseases-related procedure and brain CT, these procedures let us to early detect brain lesion. In similar indication, the brain CT is a popular examination for resolving the critical neurological patients at emergency department in Taiwan. These feasible brain CT examinations in practice, increasing the early detection of the brain tumor [ 28 ]. Moreover, the colchicine users have the higher frequency of the alcohol-related diseases, hypertension and hyperlipidemia. These comorbidities combined with the overactivity of NLRP3 inflammasome attenuating the auxiliary anti-tumor effect of colchicine in patients with MD [ 23 , 29 ]. Therefore, these combination factors (age, comorbidities and detection bias) leading to higher aHR for brain tumor in the MD with colchicine user [ 30 ]. Another important finding in this report is that the male and aged < 65 years having the colchicine users were associated with the lower aHR of colorectal cancer among the MD–colitis groups [ 12 , 31 ]. As mention before, the NLRP3 inflammasome could play a positive role for protecting the colorectal cancer (negative effect on the aHR) in the late stage of chronic colitis. In the young male with high level of the NLRP3 inflammasome activity especially the MD-colitis patients, the testosterone could modulate the NLRP3 inflammasome activity and promoting the NLRP3 inflammasome–related tumor genesis activity [ 23 ]. However, the colchicine could impair testosterone synthesis and attenuating the effect the testosterone on the NLRP3 inflammasome–related tumor genesis activity, leading to colchicine may play a positive role for protecting the cancer formation (negative effect on the aHR) [ 32 ]. Taken these together, the colchicine users were associated with the optimal counterbalance effect on the NLRP3 inflammasome, thus the young male patients in the colchicine users were associated with the lower risk of the colorectal cancer (negative effect on the aHR) in a later course of the chronic colitis even with the higher frequency of the comorbidities (Table 4 , 5 ) [ 32 , 33 ]. Similar to that, the colchicine could modulate the NLRP3 inflammasome among the female, leading to colchicine users were associated with the lower aHR for colorectal cancer [ 21 ]. The chronic colitis is a key factor of the colorectal cancer. In previous study, the colchicine may play an auxiliary for management of the chronic colitis such as Crohn’s disease with amyloidosis in young adult, perhaps leading to the lower risk of the colorectal cancer in accordance with our findings [ 3 , 34 , 35 ]. In summary, age, sex, comorbidities and detection bias are confounding factors for the effect of colchicine on cancer especially for brain tumor. However, the colchicine users having the lower risk of the colorectal cancers, especially in young adults and long-term use (> 100 days). Altogether, colchicine users are more likely to engage in health-seeking behaviors than colchicine nonusers. Meanwhile, those colchicine users who often use other medications such as anti-hypertension, statins and oral sugar or insulin sometimes forego preventive services such as cancer screening. Differential screening rates by colchicine use could then inflate the aHR for the tumor such as the brain tumor. It is to be noted that when we interpret these findings, we need to take these confounding factors into account [ 28 , 36 ]. Further research is warranted to confirm these observations. Strengths This is the first general population study to investigate the effect of colchicine on the development of cancer in patients with the MD-colitis. The time-dependent and propensity score matching for avoiding the bias. Furthermore, in Taiwan, diagnoses of the cancer and the MD follow strict guidelines. The role of colchicine in NLRP3 inflammasome activity has been examined in a Taiwanese’s study [ 37 ]. The diagnosis, treatment, or follow-up of these groups of patients drawn from the NHIRD were based on previous experiments. The strict policy contributing to our result would be representative of the real world in the Taiwan. However, the result in our study warrant future research into the relationship between cancer, and the MD-colitis. Limitations This study had a few limitations. First, the NHIRD provides no detailed information on patients regarding factors such as their lifestyle, body mass index (or obesity), habits (e.g., smoking, alcoholic drinking), physical activity, socioeconomic status, or family history; all of which are possible confounding factors in this study. We used alcohol-related diseases as a proxy for drinking, tobacco use and COPD for smoking, gout, hypertension and hyperlipidemia for exercise and life style [ 38 , 39 ]. Yet, there are gap between the proxy and real word. Second, the diagnosis of MD in Taiwan is based on clinical history, imaging, laboratory data and pathology. The coding of the MD in the NHIRD was established according to these strict standard [ 38 , 39 ]. Notably, the registries in the NHI claims are primarily used for administrative billing and are not verified for scientific purposes. Third, recording of cancer diagnoses and survival estimates based on these diagnosis codes in the NHI database are generally consistent with the National Cancer Registry (NCR) [ 40 ]. However, lack of individual laboratory data, imaging finding, and pathologic result (such as cancer staging) in the NHIRD may be the other study limitation. Forth, the retrospective study is usually lower evidence than the randomized controlled trials because a retrospective study is subject to have many unknown or uncontrolled confounding factors. Fifth, the incidence of some specific cancers was relatively low, thus limiting the power of our study. Sixth, as mention before, detection bias is present when the exposure (e.g., newly diagnosed patients with the MD leads to higher detection of the outcome of interest (cancer) due to the increased frequency of clinic visits, which also results in an overestimation of risk-cancer. Thus, including a lag period, such as starting follow-up after 1 year of the initiation of a drug in this study, simultaneously considers a latency period while also minimizing protopathic and detection bias. However, colchicine use may just indicate developments arounds an imminent cancer diagnosis, these two bias were another limitation in this study. Conclusion This study implied colchicine with an auxiliary role for protecting colorectal cancer formation in patients with MD. However, age, sex comorbidities and detection bias may modulate the aHRs for brain and colorectal cancer in the colchicine users among the MD. Abbreviations aHRs: adjusted hazard ratios; CIs: confidence intervals; NLRP3: NOD-like receptor protein 3; IL: interleukin; ICD-9-CM: International Classification of Diseases, Ninth revision, Clinical Modification; NHIRD: National Health Insurance Research Database; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; ATC: Anatomical Therapeutic Chemical; PH: proportional hazards; OSs: oral steroids; NSAIDs: non-steroidal anti-inflammatory drugs Declarations Author contributions: All authors have contributed significantly, and that all authors are in agreement with the content of the manuscript: Conception and design: Jun-Jun Yeh, Pei-Xuan Liw, Wong Yi-Sin, Husan-Min Kao, Chia-Hsun Lee, Administrative support: Chia-Hung Kao. Collection and assembly of data: All authors. Data analysis and interpretation: All authors. Manuscript writing: All authors. Final approval of manuscript: All authors. Acknowledgments: This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW111-TDU-B-212-124004), China Medical University Hospital (DMR-113-048, DMR-113-060, DMR-113-061, DMR-111-105); Ministry of Science and Technology (MOST 110-2321-B-039-003). We are grateful to the Health Data Science Center, China Medical University Hospital for providing administrative, technical, and funding support. Ditmanson Medical Foundation Chia-Yi Christian Hospital Research Program (R112-016) Conflicts of Interest: The authors declare that they have no conflicts of interest. Ethical Approval: This study was approved to fulfill the condition for exemption by the Institutional Review Board (IRB) of China Medical University & Hospital Research Ethics Center (CMUH104-REC2-115[CR-7]). The IRB also specifically waived the consent requirement. Funding: None. 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Time-dependent propensity-matched general population study of the effects of statin use on cancer risk in an interstitial lung disease and pulmonary fibrosis cohort. BMJ Open 2021; 11: e047039. Yeh JJ, Lin CL, Hsu NH, et al. Effects of statins and steroids on coronary artery disease and stroke in patients with interstitial lung disease and pulmonary fibrosis: A general population study. PLoS One 2021; 16: e0259153. Kao WH, Hong JH, See LC, et al. Validity of cancer diagnosis in the National Health Insurance database compared with the linked National Cancer Registry in Taiwan. Pharmacoepidemiol Drug Saf. 2018; 27: 1060–1066. Tables Table 1. Demographic characteristics and comorbidities in the propensity-score-matched cohorts with and without colchicine used among patients with the musculoskeletal system and connective tissue and rheumatism-related diseases. No Matched Propensity Score Matched Variable Colchicine p -value Colchicine p -value No Yes No Yes N = 76224 N =22464 N = 16026 N =16026 Age, year <0.001 0.06 ≤ 49 37581(49.3) 8818(39.3) 6073(37.9) 6279(39.2) 50-64 24818(32.6) 7828(34.9) 6009(37.5) 5870(36.6) 65+ 13825(18.1) 5818(25.9) 3944(24.6) 3877(24.2) Median±(IQR) † 50.3(38.5-60.8) 54.0(43.8-65.4) 53.7(43.7-64.6) 54.3(44.1-64.8) 0.001* Sex <0.001 0.001* Female 44370(58.2) 7884(35.1) 7700(48.1) 7138(44.5) Male 31854(41.8) 14580(64.9) 8326(52.0) 8888(55.5) Comorbidities Alcohol-related illness 30956(40.6) 11856(52.8) <0.001 8364(52.2) 8550(53.4) 0.04* CAD 1860(2.44) 1136(5.06) <0.001 575(3.59) 597(3.73) 0.51 Diabetes 11059(14.5) 4860(21.6) <0.001 3138(19.6) 3285(20.5) 0.04* Hypertension 40059(52.6) 16264(72.4) <0.001 10965(68.4) 11157(69.6) 0.02* Hyperlipidemia 49968(65.6) 18081(80.5) <0.001 12942(80.8) 12784(79.8) 0.03* COPD 5366(7.04) 3872(17.2) <0.001 2020(12.6) 2016(12.6) 0.95 Stroke 5878(7.71) 2795(12.4) <0.001 1731(10.8) 1684(10.5) 0.39 Depression 10193(13.4) 15754(70.1) <0.001 9318(58.1) 9316(58.1) 0.98 Tobacco use 5878(7.71) 2795(12.4) <0.001 1856(11.6) 1874(11.7) 0.75 Chronic kidney disease Charleson Co-morbidity index ≧1 5258(6.90) 26500(34.6) 2365(10.5) 11400(50.6) <0.001 <0.001 1544(9.63) 7600(47.4) 1517(9.47) 7578 (47.2) 0.61 0.96 Medications Acetylcysteine 7914(10.4) 3034(13.5) <0.001 2066(12.9) 2045(12.8) 0.73 smoking cessation-related 3611(4.74) 1598(7.11) <0.001 982(6.13) 938(5.85) 0.30 Anti-inflammatory and immunosuppressant drugs 34654(45.5) 14619(65.1) <0.001 9192(57.4) 9691(60.5) 0.01* Chi-square test; † : Mann-Whitney test CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; Anti-inflammatory and immunosuppressant drugs: oral steroids,aspirin, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, azathioprine, sulfasalazine, cyclophosphamide, methotrexate, hydroxychloroquine, cyclosporine *p<0.05 Table 2. Incidence of individual cancer (per 1,000 person-years) and estimated hazard ratios in the musculoskeletal system and connective tissue and rheumatism-related diseases with colchicine compared to the musculoskeletal system and connective tissue and rheumatism-related diseases without colchicine by Cox proportional hazard model with time-dependent covariates in propensity-score-matched cohorts. colchicine No (N= 16026 ) Yes (N= 16026 ) Site of cancers Event Rate # Event Rate # Crude HR (95 % CI) Adjusted HR† (95 % CI) Hematologic malignancy 55 0.44 40 0.33 1.14(0.60, 2.17) 1.00(0.58, 2.14) Head and neck cancer 49 0.40 43 0.48 1.12(0.92, 3.44) 1.11(0.85, 3.03) Esophagus 23 0.19 18 0.15 1.37(0.53, 3.55) 1.07(0.52, 3.63) Stomach 50 0.40 41 0.43 2.32(0.96, 3.97) 2.17(0.92, 3.77) Colorectal cancer 170 1.37 39 0.27 0.87(0.72,0.97)* 0.52(0.49,0.89)* Liver 123 0.99 109 0.89 1.47(0.98, 2.20) 1.08(0.85, 1.92) Pancreas 21 0.17 16 0.13 2.07(0.83, 5.12) 0.91(0.74, 4.70) Lung 120 0.97 102 0.83 1.24(0.81, 1.91) 0.85(0.76, 1.83) Skin 19 0.15 17 0.14 1.60(0.56, 4.59) 0.74(0.50, 4.30) Breast cancer 70 1.13 56 0.98 1.29(0.65, 2.55) 0.86(0.66, 2.67) Immune-related cancers 174 1.41 141 1.15 1.16(0.79, 1.69) 0.84(0.71, 1.52) Cervix 17 0.28 16 0.28 - - Endometrium 23 0.37 10 0.18 - - Ovary 11 0.18 4 0.07 1.34(0.18, 10.2) 1.02(0.21, 13.1) Prostate 67 1.08 48 0.73 1.20(0.70, 2.05) 0.97(0.68, 2.02) Bladder, kidney 72 0.58 63 0.51 1.74(1.05, 2.87) 0.99(0.94, 2.64) Brain 4 0.03 2 0.02 5.96(1.08, 33.0)* 8.42(1.32, 53.9)* Thyroid 21 0.17 16 0.13 0.61(0.15, 2.56) 0.80(0.20, 3.66) Others 43 0.35 32 0.26 0.87(0.37, 2.03) 0.83(0.36, 1.99) Rate # , incidence rate, per 1,000 person-years; Crude HR, relative hazard ratio; †Adjusting for age, sex, comorbidities and medications; *p<0.05, **p<0.01 Table 3. Incidence and adjusted hazard ratio of colorectal cancer stratified by duration of colchicine therapy in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases in the propensity score matched cohort. Medication exposed N Event Person-year Rate Adjusted HR (95% CI)† Colorectal cancer Colchicine # Non-colchicine 16026 170 123693 1.37 1.00 >15 ≤ 20 days 8099 18 61764 1.10 0.81(0.61, 1.08) 21-100 days 4036 13 30949 0.80 0.58(0.45, 0.99)* >100 days 3891 8 30096 0.23 0.17(0.15, 0.66)** # The cumulative use day are partitioned in to 3 segments by median, and third quartile Adjusted HR†: multivariable analysis including age, sex, comorbidities and medications; *p<0.05, **p<0.01 Table 4. Incidence and hazards ratio of colorectal cancer measured by age, sex, comorbidities and medications in the propensity-score-matched cohorts by Cox proportional hazard models with time-dependent exposure covariates among the musculoskeletal system and connective tissue and rheumatism-related diseases. Propensity Score Matched Colchicine No (N= 16026 ) Yes (N= 16026 ) Variables Event Rate # Event Rate # Adjusted HR† (95% CI) Colorectal cancer Age, years ≤ 49 22 0.43 9 0.17 0.27(0.12,0.83)** 50-64 82 1.78 18 0.47 0.79(0.40, 0.59)** 65+ 66 2.49 12 0.75 0.88(0.36, 3.49) Sex Female 71 1.15 23 0.56 0.47(0.31, 0.66)** Male 99 1.60 16 0.79 0.61(0.55, 0.89)* Rate # , incidence rate, per 1000 person-years; Adjusted HR†: multivariable analysis including age, sex, comorbidities and medications; *p<0.05; **p<0.01 Table 5. Summary findings and speculations. Without stratification with age and sex. NLRP3 1 2 3 4 ¥♥ aHR ※※ -Protecting in chronic colitis NLRP3 Dual Effect For Cancer Colchicine Modulate NLRP3 Effect For Cancer Hyperlipidemia Hypertension Diabetes Liver cirrhosis Detection Bias Modulate aHR effect of 1+2+3+4 = Colorectal cancer –MD colitis +/- --- + 0/+ ▬ Stratification with Age and Sex. NLRP3 Effect for Cancer Testosterone (+) Estrogen (?) Effect For Cancer Hyperlipidemia Hypertension Diabetes Tobacco use Colchicine Modulate NLRP3 Effect for Cancer aHR ※※ effect of 1+2+3+4 = ♥ Colorectal cancer Male + + + --- ▬ Female + ? + --- ▬ >65-year + 0 + 0/- 0 <65-year + + + --- ▬ + were associated with enhancing the +aHR, -were associated with attenuating-aHR,0 were null effect on the aHR aHR ※※ effect of 1+2+3+4 MD, the musculoskeletal system and connective tissue and rheumatism-related diseases ¥ The colchicine users have received the higher frequency of medical services (N ≧ 4) with the at least one procedure in relation to cancer diagnosis on these cancers than the colchicine nonusers (N=1) ♥ In colchicine users, the frequency of high up to 43.2% patients in brain cancer cohort have receved the brain–related procedure for neurodegenerative diseases or head trauma. In contrast, in colorectal cancer cohort, only13% patients have received the colonscopy-related procedure. However, these colchicine users having the higher frequency of the examination of the cancers-related procedures than the colchicine non-users before the diagnosis of these cancers. Additional Declarations No competing interests reported. Supplementary Files SupplementalTable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Feb, 2024 Reviews received at journal 06 Feb, 2024 Reviewers agreed at journal 02 Feb, 2024 Reviewers agreed at journal 28 Jan, 2024 Reviewers invited by journal 28 Dec, 2023 Editor assigned by journal 27 Dec, 2023 Submission checks completed at journal 26 Dec, 2023 First submitted to journal 21 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3789273","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264087961,"identity":"c1efecd5-aad7-4627-8aae-4df0de703e6e","order_by":0,"name":"Jun-Jun Yeh","email":"","orcid":"","institution":"Ditmanson Medical Foundation Chia-Yi Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jun-Jun","middleName":"","lastName":"Yeh","suffix":""},{"id":264087964,"identity":"b13032e5-945f-46db-b7fb-df9b6e623621","order_by":1,"name":"Pei-Xuan Liw","email":"","orcid":"","institution":"Ditmanson Medical Foundation Chia-Yi Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pei-Xuan","middleName":"","lastName":"Liw","suffix":""},{"id":264087965,"identity":"d546ab56-9b3a-4874-a76f-52a2826a28f4","order_by":2,"name":"Yi-Sin Wong","email":"","orcid":"","institution":"Ditmanson Medical Foundation Chia-Yi Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi-Sin","middleName":"","lastName":"Wong","suffix":""},{"id":264087969,"identity":"cc8012a8-b208-48ff-97c2-c476e858a59b","order_by":3,"name":"Husan-Min Kao","email":"","orcid":"","institution":"Ditmanson Medical Foundation Chia-Yi Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Husan-Min","middleName":"","lastName":"Kao","suffix":""},{"id":264087972,"identity":"8411eb58-9657-4379-81ba-8e0543b61bb0","order_by":4,"name":"Chia-Hsun Lee","email":"","orcid":"","institution":"Ditmanson Medical Foundation Chia-Yi Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chia-Hsun","middleName":"","lastName":"Lee","suffix":""},{"id":264087975,"identity":"d2113bd6-9b6b-4a9d-a567-d721656fea12","order_by":5,"name":"Cheng-Li Lin","email":"","orcid":"","institution":"China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Cheng-Li","middleName":"","lastName":"Lin","suffix":""},{"id":264087977,"identity":"629b07bc-0d6f-4048-9979-62bcc4d90933","order_by":6,"name":"Chia-Hung Kao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYDCCAwzMICqBjYEHRNsAMWPjAVK0pIG0NBCnhQGi5TBUEA/gu32A2eBHhV0eH/vZY9IFv87brW0/DLSlxiYalxbJcwnMiT1nkovZePLSpGf23U7ediYRqOVYWm4DDi0GZxiYD/C2HUhsY8gxk+btuZ1sdgCohbHhMF4tB/+CtPC/AWk5l2x2/iFhLclgWySAtvD8OGBndoOALZJnGJuNZc4kA7W8MbbmbUhOMLsBtCUBj1/4zjAflnxTYZc4vz/H8DbPHzt7s/PpDx98qLHBqQUUcUjsNoZEMDcBp3IM8IfBnnjFo2AUjIJRMFIAAHqDYp2fchBNAAAAAElFTkSuQmCC","orcid":"","institution":"China Medical University","correspondingAuthor":true,"prefix":"","firstName":"Chia-Hung","middleName":"","lastName":"Kao","suffix":""}],"badges":[],"createdAt":"2023-12-22 00:59:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3789273/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3789273/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49077659,"identity":"5778453b-203a-4012-abf3-14948110d769","added_by":"auto","created_at":"2024-01-02 19:09:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":298714,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of colorectal cancer curves for colchicine users and colchicine non-users by propensity score matched.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-3789273/v1/44f4c2bb46c4bac8da53325f.png"},{"id":49078498,"identity":"54097d50-ac16-4d5f-86a6-e79aee791aca","added_by":"auto","created_at":"2024-01-02 19:17:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":775837,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3789273/v1/c93a1433-874f-4ed0-946c-a8aaf1319695.pdf"},{"id":49077660,"identity":"20312c80-b7d9-4d6b-9030-cda3bb60edd9","added_by":"auto","created_at":"2024-01-02 19:09:25","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19819,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-3789273/v1/0ef2f532824d8932a1d94ad7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of colchicine on cancer risk in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe pyrin domain\u0026ndash;containing protein 3 (or NOD-like receptor protein 3 [NLRP3]) inflammasome and NLRP3 inflammasome related cytokines -interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6) have been associated with colorectal cancer formation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Notably, these markers would increase, especially in patients with the gout, diabetes, obesity and cancer [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The role of the NLRP3 inflammasome varies according to sex, age, and tumor type. For example, estrogen enhances the expression of NLRP3 inflammasome, whereas testosterone inhibits its expression. The estrogen acts through estrogen receptor β (ERβ) to enhance the activation of NLPR3 inflammasome and promote the progression of endometrial cancer [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Similarly, NLRP3 inflammasome protects against the bowel inflammation associated-tumor formation in chronic stages but promotes colon cancer in the early stage of the colitis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In contrast, Zaki et al study the consequence of a decrease in IL-18 in mice lacking components of the NLRP3 inflammasome, resulting in higher mortality rates. Thus, the NLRP3 inflammasome may be critically involved in the maintenance of intestinal homeostasis and protection against colitis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Hence, NLRP3 inflammasome exhibits contrasting roles in cancer development [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eColchicine is an anti-inflammatory drug, it have been used in the gout and nongout conditions such as arthritis-\u003cb\u003ec\u003c/b\u003erystal arthropathies, systemic inflammatory diseases such as sarcoidosis, Behcet's syndrome, autoimmune disease, chronic idiopathic or spontaneous urticarial skin diseases, allergic purpura, psoriasis, collagen vascular diseases, and cardiovascular -related diseases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In addition, colchicine exerts its unique effects by the retardation of new tubulin formation, dissociation of tubulin, thus leading to cancer cell death. In addition, colchicine inhibits angiogenesis and cancer cell migration and metastasis, limits ATP influx into mitochondria, and releases caspases and cytochrome-c, thus leading to apoptosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Colchicine could also inhibit neutrophil function, and attenuate expression of IL-6 and NLRP3 inflammasome. Altogether, colchicine could play an auxiliary role in the prevention of cancer in patients with gout [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe important evidence that links inflammation and cancer is that nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, reduce the risk and mortality from many cancers. In recent study, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The musculoskeletal system and connective tissue and rheumatism-related diseases (MD) such as the gout, autoimmune disease (eg, ulcerative colitis, Crohn\u0026rsquo;s disease), psoriasis are associated with the risk of cancer. However, rare research has examined the role of colchicine in the evolution of cancer among patients with MD. Thus, in this study, we investigated the effect of colchicine on the development of cancer in patients with MD by using a general population design.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData source\u003c/h2\u003e \u003cp\u003eWe analyzed the Longitudinal Health Insurance Database, a subset of the NHIRD that contains demographic information, inpatient and outpatient records, medications, and treatments of 2\u0026nbsp;million insured individuals.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eExcluding criteria including: patients younger than 20 years old, with previous history of cancer (\u003cem\u003eICD-9-CM\u003c/em\u003e codes 140\u0026ndash;239), as well as those with additional indications for colchicine treatment (eg, Bechet\u0026rsquo;s disease) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Including criteria as below: patients who used colchicine between 2000 and 2012 were defined as colchicine users among patients with MD [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. And, these patients had at least two outpatients visits or an inpatient visit. The colchicine users need fulfill criteria as below: 1) In Lin et study, the nude mice experiment showed that colchicine-treated mice after 14 days of treatment had lower increased tumor volume ratios and tumor growth rates than the control. In accordance with this previous study, we set the duration of the colchicine use\u0026thinsp;\u0026gt;\u0026thinsp;15 days [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]; 2) Incident use of drugs increases in the months prior to a cancer diagnosis. To avoid reverse causation, 6 months\u0026rsquo; lag time would be sufficient for most drug-cancer associations. In this study, to avoid this reverse causation, the lag time would be set as ≧\u0026thinsp;12 months from the first prescription of colchicine to any diagnosis of cancer [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Nonusers defined as those who never used colchicine or prescriptions within 12 months of diagnosis of cancer were not considered as exposed, again to avoid reverse causation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. For those who had more than one prescription of immunosuppressants, a minimum of 7 days between prescriptions was required.\u003c/p\u003e \u003cp\u003eOwing to this a time-dependent study, the index date for the colchicine users was the date of the first prescription of colchicine, and a date between 2000 and 2012 was the index date for the non-users. Colchicine users and nonusers were then matched by propensity scores according to age, sex, comorbidities, medications and index date. The \u003cem\u003eInternational Classification of Diseases, Ninth Revision, Clinical Modification\u003c/em\u003e (\u003cem\u003eICD-9-CM\u003c/em\u003e) diagnosis codes considered for patients with the MD. (Full names, \u003cb\u003eSupplemental Table\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eLicensing Committee (Ethics Statement)\u003c/h2\u003e \u003cp\u003eThe NHIRD encrypts patient personal information to protect privacy and provides researchers with anonymous identification numbers associated with relevant claims information, including sex, date of birth, medical services received, and prescriptions. All methods were carried out in accordance with relevant guidelines and regulations. Therefore, patient consent is not required to access the NHIRD. This study was approved to fulfill the condition for exemption by the Institutional Review Board (IRB) of China Medical University \u0026amp; Hospital Research Ethics Center (CMUH104-REC2-115[CR-7]). The IRB also specifically waived the consent requirement.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData Availability Statement\u003c/h2\u003e \u003cp\u003eThe dataset used in this study is held by the Taiwan Ministry of Health and Welfare (MOHW). The Ministry of Health and Welfare must approve our application to access this data. Any researcher interested in accessing this dataset can submit an application form to the Ministry of Health and Welfare requesting access. Please contact the staff of MOHW (Email: [email protected]) for further assistance. Taiwan Ministry of Health and Welfare Address: No.488, Sec. 6, Zhongxiao E. Rd., Nangang Dist., Taipei City 115, Taiwan (R.O.C.). Phone: +886-2-8590-6848. All relevant data are within the paper.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eMain outcome and covariates\u003c/h2\u003e \u003cp\u003eThe primary endpoint of this study was the development of cancer (\u003cem\u003eICD-9-CM\u003c/em\u003e codes 140\u0026ndash;239), as evidenced by a major illness or injury certificate of cancer. The study endpoint was defined as the occurrence of cancer, withdrawal from the insurance program, or December 31, 2013. In addition to age and sex, other potential confounders included comorbidities (Full names, \u003cb\u003eSupplemental Table\u0026nbsp;1\u003c/b\u003e). The use of acetylcysteine, smoking cessation\u0026ndash;related medication, anti-inflammatory drugs (aspirin, NSAID) and immunosuppressant drugs was evaluated as a confounder also. The severity and duration of MD have impact on the risk of cancer. Owing to the comorbidities and medications were close relation to the MD severity and duration [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Thus, these comorbidities, medications and Charleson Co-morbidity index enter into analysis in this study. Meanwhile, we used alcohol related diseases as a proxy for drinking, chronic obstructive pulmonary disease (COPD) and tobacco use for smoking, gout and hypertension and hyperlipidemia for exercise and life style [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The Anatomical Therapeutic Chemical code (ATC) of medications were defined as a prescription with one of the following National Health Insurance (NHI) codes: (\u003cb\u003eSupplemental Table\u0026nbsp;1).\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were expressed as number and percentage, and differences between the two cohorts were examined using the chi-square test. Continuous variables were presented as median and interquartile range, and differences between the two cohorts were assessed using the Mann\u0026ndash;Whitney U test. The incidence rate was expressed as per 1,000 person-years. The disease duration might impact on the risk of cancer and should be taken into account. Thus, the Cox proportional hazards (PH) model with time-dependent exposure covariates was used as the main model in the study to analyze the effect of colchicine on cancer. The association between the duration of colchicine use and the development of cancer was analyzed using the general Cox PH model. The Kaplan-Meier method was used to obtain the cumulative curves, and the results were then examined using the log-rank test. SAS statistical software (version 9.1, SAS Institute, Cary, NC) was used to perform the analysis. A p-value less than .05 was set as the significant level.\u003c/p\u003e \u003c/div\u003e"},{"header":"Result","content":"\u003cp\u003eA total of 22,464 patients were defined as colchicine users in this study (\u003cstrong\u003eTable 1\u003c/strong\u003e). The median age of the colchicine users was higher than that of the colchicine nonusers: 54.3 years versus 53.7 years, respectively. A male preponderance was observed in the colchicine users compared with the colchicine nonusers.\u0026nbsp;As this is a time-dependent study, more patients had developed comorbidities such as alcohol-related diseases, diabetes, hypertension and hyperlipidemia in the colchicine users than in the colchicine nonusers. In addition, the colchicine users included more patients who used acetylcysteine,\u0026nbsp;smoking cessation-related\u0026nbsp;medication, anti-inflammatory drugs such as oral steroids (OSs),\u0026nbsp;non-steroidal anti-inflammatory drugs (NSAIDs),\u0026nbsp;acetylsalicylic acid,\u0026nbsp;and immunosuppressant drugs such as\u0026nbsp;azathioprine, sulfasalazine, cyclophosphamide, methotrexate, hydroxychloroquine, and cyclosporine. After propensity score matching, both cohorts included 16,026 patients each. Both cohorts had a similar distribution of age, sex, comorbidities, and medications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e illustrates the association of colchicine use with different types of cancer in the colchicine users. Compared with colchicine nonusers, the colorectal cancer and brain tumor in the colchicine users were associated with the different adjusted HRs [aHRs], the aHRs (95 % CI) were 0.52 (0.49, 0.89), and 8.42 (1.32, 53.9)), respectively. The colchicine users were associated with the lower incidence of the colorectal cancer \u003cstrong\u003e(Figure 1)\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eillustrates the colchcine use with \u0026gt;20 days having the lower aHR for the colorectal cancer. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInvestigate the impact of the sex and age on the cancers formation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe elderly with colchicine use having the null effect for the aHR of colorectal cancer. Regarding the young adult, the aHRs for colorectal cancer were associated with the lower aHRs for the colchicine users.\u003cstrong\u003e\u0026nbsp;(Table 4)\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003cstrong\u003eovariates in proxies to the NLRP3 expression for the incident cancer.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe NLRP3 expression were unavailable in the NHIRD. However, the NLRP3 expression in accordance with the cell type, duration of use, age, sex. Meanwhile, these variables were independent and critical factors of the colchicine on the cancer promotion [14, 20-23]. Moreover, those covariates such as comorbidities (eg, alcohol-related disease, hypertension, diabetes, depression, tobacco use) in proxies to the NLRP3 expression for the incident cancer [21, 24]. Therein, these variants were entered into the analysis [1, 25]. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity analysis -\u0026nbsp;Propensity score analysis for time-dependent exposure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIn different cell line and comorbidities\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe colchicine users have the higher aHR of brain tumor and lower aHR of colorectal cancer. Combination of the\u0026nbsp;NLRP3 dual effect for cancer,\u0026nbsp;colchicine modulates NLRP3 effect for cancer, duration of drug effect and detection bias could play a role for contributing to these results. We did sensitivity analysis for clarifying these points for colorectal cancer. \u003cstrong\u003e(Table 4, 5)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eWe displayed these speculations in the \u003cstrong\u003eTable 5\u003c/strong\u003e: 1) the combination the effect of the colchicine, NLRP3, comorbidities and detection bias on the risk of cancer in colorectal cancer with chronic colitis; 2) sex and age for modulation the effect of the colchicine on the risk of colorectal cancer [26, 27].\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe main finding of our study was that colchicine use was associated with a lower risk of the colorectal cancer in patients with the MD. The Kaplan\u0026ndash;Meier was used only one variable (event of interest-colchicine use) for estimating the survival curves. Log rank test compares two or more survival curves and does not consider additional independent variables. Similar to multiple regression model, Cox PH model considers additional independent variables (covariates-age, sex, comorbidities) for estimating the differences between the survival curves. To the best of our knowledge, this study is the first study to report an association between colchicine use and incidental cancers in patients with the MD, who were associated with the lower risk of colorectal cancer based on the Cox PH model with time-dependent exposure. Similar to that, the colchicine users were associated with the lower cumulative incidence of the colorectal cancer in analysis of the Kaplan-Meier method.\u003c/p\u003e \u003cp\u003eAn important confounding factor of this study is the detection bias. Detection bias is hypothesized, in part, because of observed differences between the colchicine users and colchicine nonusers. Detection bias occurs when screening and diagnostic patterns vary in association with potential risk factors. Detection bias could exaggerate or attenuate estimated cancer-colchicine associations and affecting the aHR for cancer. For example, the aged\u0026thinsp;\u0026gt;\u0026thinsp;65 received the higher frequency of neurodegenerative diseases-related procedure and brain CT, these procedures let us to early detect brain lesion. In similar indication, the brain CT is a popular examination for resolving the critical neurological patients at emergency department in Taiwan. These feasible brain CT examinations in practice, increasing the early detection of the brain tumor [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMoreover, the colchicine users have the higher frequency of the alcohol-related diseases, hypertension and hyperlipidemia. These comorbidities combined with the overactivity of NLRP3 inflammasome attenuating the auxiliary anti-tumor effect of colchicine in patients with MD [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Therefore, these combination factors (age, comorbidities and detection bias) leading to higher aHR for brain tumor in the MD with colchicine user [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnother important finding in this report is that the male and aged\u0026thinsp;\u0026lt;\u0026thinsp;65 years having the colchicine users were associated with the lower aHR of colorectal cancer among the MD\u0026ndash;colitis groups [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. As mention before, the NLRP3 inflammasome could play a positive role for protecting the colorectal cancer (negative effect on the aHR) in the late stage of chronic colitis. In the young male with high level of the NLRP3 inflammasome activity especially the MD-colitis patients, the testosterone could modulate the NLRP3 inflammasome activity and promoting the NLRP3 inflammasome\u0026ndash;related tumor genesis activity [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, the colchicine could impair testosterone synthesis and attenuating the effect the testosterone on the NLRP3 inflammasome\u0026ndash;related tumor genesis activity, leading to colchicine may play a positive role for protecting the cancer formation (negative effect on the aHR) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Taken these together, the colchicine users were associated with the optimal counterbalance effect on the NLRP3 inflammasome, thus the young male patients in the colchicine users were associated with the lower risk of the colorectal cancer (negative effect on the aHR) in a later course of the chronic colitis even with the higher frequency of the comorbidities (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Similar to that, the colchicine could modulate the NLRP3 inflammasome among the female, leading to colchicine users were associated with the lower aHR for colorectal cancer [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe chronic colitis is a key factor of the colorectal cancer. In previous study, the colchicine may play an auxiliary for management of the chronic colitis such as Crohn\u0026rsquo;s disease with amyloidosis in young adult, perhaps leading to the lower risk of the colorectal cancer in accordance with our findings [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn summary, age, sex, comorbidities and detection bias are confounding factors for the effect of colchicine on cancer especially for brain tumor. However, the colchicine users having the lower risk of the colorectal cancers, especially in young adults and long-term use (\u0026gt;\u0026thinsp;100 days).\u003c/p\u003e \u003cp\u003eAltogether, colchicine users are more likely to engage in health-seeking behaviors than colchicine nonusers. Meanwhile, those colchicine users who often use other medications such as anti-hypertension, statins and oral sugar or insulin sometimes forego preventive services such as cancer screening. Differential screening rates by colchicine use could then inflate the aHR for the tumor such as the brain tumor. It is to be noted that when we interpret these findings, we need to take these confounding factors into account [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Further research is warranted to confirm these observations.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eStrengths\u003c/h2\u003e \u003cp\u003eThis is the first general population study to investigate the effect of colchicine on the development of cancer in patients with the MD-colitis. The time-dependent and propensity score matching for avoiding the bias. Furthermore, in Taiwan, diagnoses of the cancer and the MD follow strict guidelines. The role of colchicine in NLRP3 inflammasome activity has been examined in a Taiwanese\u0026rsquo;s study [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The diagnosis, treatment, or follow-up of these groups of patients drawn from the NHIRD were based on previous experiments. The strict policy contributing to our result would be representative of the real world in the Taiwan. However, the result in our study warrant future research into the relationship between cancer, and the MD-colitis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study had a few limitations. First, the NHIRD provides no detailed information on patients regarding factors such as their lifestyle, body mass index (or obesity), habits (e.g., smoking, alcoholic drinking), physical activity, socioeconomic status, or family history; all of which are possible confounding factors in this study. We used alcohol-related diseases as a proxy for drinking, tobacco use and COPD for smoking, gout, hypertension and hyperlipidemia for exercise and life style [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Yet, there are gap between the proxy and real word. Second, the diagnosis of MD in Taiwan is based on clinical history, imaging, laboratory data and pathology. The coding of the MD in the NHIRD was established according to these strict standard [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Notably, the registries in the NHI claims are primarily used for administrative billing and are not verified for scientific purposes. Third, recording of cancer diagnoses and survival estimates based on these diagnosis codes in the NHI database are generally consistent with the National Cancer Registry (NCR) [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. However, lack of individual laboratory data, imaging finding, and pathologic result (such as cancer staging) in the NHIRD may be the other study limitation. Forth, the retrospective study is usually lower evidence than the randomized controlled trials because a retrospective study is subject to have many unknown or uncontrolled confounding factors. Fifth, the incidence of some specific cancers was relatively low, thus limiting the power of our study. Sixth, as mention before, detection bias is present when the exposure (e.g., newly diagnosed patients with the MD leads to higher detection of the outcome of interest (cancer) due to the increased frequency of clinic visits, which also results in an overestimation of risk-cancer. Thus, including a lag period, such as starting follow-up after 1 year of the initiation of a drug in this study, simultaneously considers a latency period while also minimizing protopathic and detection bias. However, colchicine use may just indicate developments arounds an imminent cancer diagnosis, these two bias were another limitation in this study.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study implied colchicine with an auxiliary role for protecting colorectal cancer formation in patients with MD. However, age, sex comorbidities and detection bias may modulate the aHRs for brain and colorectal cancer in the colchicine users among the MD.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eaHRs: adjusted hazard ratios; CIs: confidence intervals; NLRP3: NOD-like receptor protein 3; IL: interleukin; ICD-9-CM: International Classification of Diseases, Ninth revision, Clinical Modification; NHIRD: National Health Insurance Research Database; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; ATC: Anatomical Therapeutic Chemical; PH: proportional hazards; OSs: oral steroids; NSAIDs: non-steroidal anti-inflammatory drugs\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors have contributed significantly, and that all authors are in agreement with the content of the manuscript:\u0026nbsp;Conception and design: Jun-Jun Yeh,\u0026nbsp;Pei-Xuan Liw,\u0026nbsp;Wong Yi-Sin,\u0026nbsp;Husan-Min Kao,\u0026nbsp;Chia-Hsun Lee,\u0026nbsp;Administrative support:\u0026nbsp;Chia-Hung Kao.\u0026nbsp;Collection and assembly of data:\u0026nbsp;All authors.\u0026nbsp;Data analysis and interpretation:\u0026nbsp;All authors.\u0026nbsp;Manuscript writing:\u0026nbsp;All authors. Final approval of manuscript: All authors.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW111-TDU-B-212-124004), China Medical University Hospital (DMR-113-048, DMR-113-060,\u0026nbsp;DMR-113-061,\u0026nbsp;DMR-111-105); Ministry of Science and Technology (MOST 110-2321-B-039-003). We are grateful to the Health Data Science Center, China Medical University Hospital for providing administrative, technical, and funding support. Ditmanson Medical Foundation Chia-Yi Christian Hospital Research Program (R112-016)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved to fulfill the condition for exemption by the Institutional Review Board (IRB) of China Medical University \u0026amp; Hospital Research Ethics Center (CMUH104-REC2-115[CR-7]). The IRB also specifically waived the consent requirement.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset used in this study is held by the Taiwan Ministry of Health and Welfare (MOHW). The Ministry of Health and Welfare must approve our application to access this data. Any researcher interested in accessing this dataset can submit an application form to the Ministry of Health and Welfare requesting access. Please contact the staff of MOHW (Email: [email protected]) for further assistance. Taiwan Ministry of Health and Welfare Address: No.488, Sec. 6, Zhongxiao E. Rd., Nangang Dist., Taipei City 115, Taiwan (R.O.C.). Phone: +886-2-8590-6848. \u0026nbsp;All relevant data are within the paper.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMissiroli S, Perrone M, Boncompagni C, et al. Targeting the NLRP3 Inflammasome as a New Therapeutic Option for Overcoming Cancer. Cancers 2021; 13: 2297.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu SG, Wu XX, Hua T, et al. NLRP3 inflammasome activation by estrogen promotes the progression of human endometrial cancer. Onco Targets Ther. 2019; 12: 6927\u0026ndash;6936.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi Y, Li J, Yang P, et al. Colchicine increases intestinal permeability, suppresses inflammatory responses, and alters gut microbiota in mice. Toxicol Lett 2020; 334: 66\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZaki MH, Boyd KL, Vogel P, et al. 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Ann Epidemiol. 2023; 84: 25\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYagyu H, Murohashi K, Hara Y, et al. Clinical utility of a composite scoring system including Charlson Comorbidity Index score in patients with interstitial lung disease. J Thorac Dis. 2020; 12: 5774\u0026ndash;5782.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarvid MS, Sidahmed E, Spence ND, et al. Consumption of red meat and processed meat and cancer incidence: a systematic review and meta-analysis of prospective studies. Eur J Epidemiol. 2021; 36: 937\u0026ndash;951.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaymakers A, Sin DD, Sadatsafavi M, et al. Statin use and lung cancer risk in chronic obstructive pulmonary disease patients: a population-based cohort study. Respir Res. 2020; 21: 118.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho JH, Joo YH, Shin EY, et al. Anticancer Effects of Colchicine on Hypopharyngeal Cancer. Anticancer Res. 2017; 37: 6269\u0026ndash;6280.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChuang JP, Lee JC, Leu TH, et al. Association of gout and colorectal cancer in Taiwan: a nationwide population-based cohort study. BMJ open 2019; 9: e028892.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim SR, Kim EK, Cho J, et al. Effect of Anti-Inflammatory Drugs on Clinical Outcomes in Patients With Malignant Pericardial Effusion. J Am Coll Cardiol. 2020; 76: 1551\u0026ndash;1561.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang H, Tang Y, Tao J. Sex-Related Overactivation of NLRP3 Inflammasome Increases Lethality of the Male COVID-19 Patients. Front Mol Biosci 2021; 8: 671363.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobinson PC, Terkeltaub R, Pillinger MH, et al. Consensus Statement Regarding the Efficacy and Safety of Long-Term Low-Dose Colchicine in Gout and Cardiovascular Disease. Am J Med. 2022; 135: 32\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei Q, Guo P, Mu K, et al. Estrogen suppresses hepatocellular carcinoma cells through ERβ-mediated upregulation of the NLRP3 inflammasome. Lab Invest. 2015; 95: 804\u0026ndash;816.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhisa M, Marinelli C, Savarino V, et al. Idiopathic pulmonary fibrosis and GERD: links and risks. Ther Clin Risk Manag 2019; 15: 1081\u0026ndash;1093.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu JP, Tsai CL, Wysham NG, et al. Chronic hypersensitivity pneumonitis in the southeastern United States: an assessment of how clinicians reached the diagnosis. BMC Pulm Med 2020; 20: 32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRussell B, Garmo H, Beckmann K, et al. A case-control study of lower urinary-tract infections, associated antibiotics and the risk of developing prostate cancer using PCBaSe 3.0. PLoS One 2018; 13: e0195690.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma BR, Kanneganti TD. NLRP3 inflammasome in cancer and metabolic diseases. Nat Immunol. 2021; 22: 550\u0026ndash;559.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu SY, Hsieh MS, Lin MY, et al. Trends of CT utilisation in an emergency department in Taiwan: a 5-year retrospective study. BMJ Open 2016; 6: e010973.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTavassoli S, Shahabinasab I, Norouzi A, et al. From bowel inflammation to the bone and joints: musculoskeletal examination in inflammatory bowel disease (IBD). BMC Musculoskelet Disord. 2021; 22: 1019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing J, Shang X, Zhang Z, et al. FDA-approved medications that impair human spermatogenesis. Oncotarget 2017; 8: 10714\u0026ndash;10725.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaimov-Kochman R, Ben-Chetrit E. The effect of colchicine treatment on sperm production and function: a review. Hum Reprod 1998; 13: 360\u0026ndash;362.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYou G, Ferges W, Das K. Infliximab and Colchicine Therapy in the Treatment of Systemic Secondary Amyloidosis in Crohn\u0026rsquo;s Disease: 1502. American Journal of Gastroenterology 2014; 109: S443.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarkhodari A, Lee KE, Shen M, et al. Inflammatory bowel disease: focus on enteropathic arthritis and therapy. Rheumatol Immunol Res. 2022; 3: 69\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng YC, Lin CL, Hsu WY, et al. The risk of colorectal cancer is related to frequent hospitalization of IBD in an Asian population: results from a nationwide study. QJM 2015; 108: 457\u0026ndash;463.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin TY, Tsai MC, Tu W, et al. Role of the NLRP3 Inflammasome: Insights Into Cancer Hallmarks. Front Immunol 2021; 11: 610492.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYeh JJ, Lai JN, Lin CL, et al. Time-dependent propensity-matched general population study of the effects of statin use on cancer risk in an interstitial lung disease and pulmonary fibrosis cohort. BMJ Open 2021; 11: e047039.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYeh JJ, Lin CL, Hsu NH, et al. Effects of statins and steroids on coronary artery disease and stroke in patients with interstitial lung disease and pulmonary fibrosis: A general population study. PLoS One 2021; 16: e0259153.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKao WH, Hong JH, See LC, et al. Validity of cancer diagnosis in the National Health Insurance database compared with the linked National Cancer Registry in Taiwan. Pharmacoepidemiol Drug Saf. 2018; 27: 1060\u0026ndash;1066.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Demographic characteristics and comorbidities in the\u0026nbsp;propensity-score-matched\u0026nbsp;cohorts with and without\u0026nbsp;colchicine\u0026nbsp;used among patients with\u0026nbsp;the musculoskeletal system and connective tissue and rheumatism-related diseases.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"781\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.224071702944943%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.321382842509603%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Matched\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.9385403329065305%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.321382842509603%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePropensity Score Matched\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.194622279129321%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.224071702944943%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.321382842509603%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eColchicine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.9385403329065305%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.321382842509603%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eColchicine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.194622279129321%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN = 76224\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN =22464\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN = 16026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN =16026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026le; 49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e37581(49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e8818(39.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e6073(37.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e6279(39.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e50-64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e24818(32.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e7828(34.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e6009(37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e5870(36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; 65+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e13825(18.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e5818(25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e3944(24.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e3877(24.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Median\u0026plusmn;(IQR)\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e50.3(38.5-60.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e54.0(43.8-65.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e53.7(43.7-64.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e54.3(44.1-64.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e44370(58.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e7884(35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e7700(48.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e7138(44.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e31854(41.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e14580(64.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e8326(52.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e8888(55.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eAlcohol-related illness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e30956(40.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e11856(52.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e8364(52.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e8550(53.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eCAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1860(2.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1136(5.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e575(3.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e597(3.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eDiabetes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e11059(14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e4860(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e3138(19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e3285(20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eHypertension\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e40059(52.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e16264(72.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e10965(68.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e11157(69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eHyperlipidemia\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e49968(65.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e18081(80.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e12942(80.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e12784(79.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e5366(7.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e3872(17.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e2020(12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e2016(12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eStroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e5878(7.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e2795(12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1731(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1684(10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e10193(13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e15754(70.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e9318(58.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e9316(58.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eTobacco use\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e5878(7.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e2795(12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1856(11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1874(11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eChronic kidney disease\u003c/p\u003e\n \u003cp\u003eCharleson Co-morbidity index\u0026nbsp;≧1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e5258(6.90)\u003c/p\u003e\n \u003cp\u003e26500(34.6) \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e2365(10.5)\u003c/p\u003e\n \u003cp\u003e11400(50.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1544(9.63)\u003c/p\u003e\n \u003cp\u003e7600(47.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1517(9.47)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;7578 (47.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eAcetylcysteine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e7914(10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e3034(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e2066(12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e2045(12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003esmoking cessation-related\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e3611(4.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e1598(7.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e982(6.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e938(5.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.28883183568678%\" valign=\"top\"\u003e\n \u003cp\u003eAnti-inflammatory and immunosuppressant drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e34654(45.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e14619(65.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.958921694480103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e9192(57.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.634146341463415%\" valign=\"top\"\u003e\n \u003cp\u003e9691(60.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.21566110397946%\" valign=\"top\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eChi-square test; \u003csup\u003e\u0026dagger;\u003c/sup\u003e: Mann-Whitney test\u003c/p\u003e\n\u003cp\u003eCAD: coronary artery disease;\u0026nbsp;COPD:\u0026nbsp;chronic obstructive pulmonary disease;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnti-inflammatory and immunosuppressant drugs: oral steroids,aspirin, non-steroidal anti-inflammatory drugs,\u0026nbsp;acetylsalicylic acid,\u0026nbsp;azathioprine,\u0026nbsp;sulfasalazine,\u0026nbsp;cyclophosphamide, methotrexate, hydroxychloroquine, cyclosporine\u003c/p\u003e\n\u003cp\u003e*p\u0026lt;0.05\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2.\u0026nbsp;Incidence of individual cancer (per 1,000 person-years) and estimated hazard ratios in\u0026nbsp;the musculoskeletal system and connective tissue and rheumatism-related diseases\u0026nbsp;with colchicine compared to the\u0026nbsp;musculoskeletal system and connective tissue and rheumatism-related diseases\u0026nbsp;without colchicine by Cox proportional hazard model with time-dependent covariates in propensity-score-matched\u0026nbsp;cohorts.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"690\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.391304347826086%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"32.89855072463768%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ecolchicine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.710144927536234%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.431059506531206%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.400580551523948%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N=\u003c/strong\u003e\u003cstrong\u003e16026\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.400580551523948%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N=\u003c/strong\u003e\u003cstrong\u003e16026\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.029027576197386%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.738751814223512%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite of cancers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRate\u003csup\u003e#\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRate\u003csup\u003e#\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude HR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95 % CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted HR\u0026dagger;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95 % CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eHematologic malignancy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.14(0.60, 2.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e1.00(0.58, 2.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eHead and neck cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.12(0.92, 3.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e1.11(0.85, 3.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eEsophagus\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.37(0.53, 3.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e1.07(0.52, 3.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eStomach\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e2.32(0.96, 3.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e2.17(0.92, 3.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eColorectal cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; 0.87(0.72,0.97)*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;0.52(0.49,0.89)*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eLiver\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.47(0.98, 2.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e1.08(0.85, 1.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003ePancreas\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e2.07(0.83, 5.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.91(0.74, 4.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eLung\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.24(0.81, 1.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.85(0.76, 1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eSkin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.60(0.56, 4.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.74(0.50, 4.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eBreast cancer\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e1.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.29(0.65, 2.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.86(0.66, 2.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eImmune-related cancers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.16(0.79, 1.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.84(0.71, 1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eCervix\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eEndometrium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eOvary\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.34(0.18, 10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e1.02(0.21, 13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eProstate\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.20(0.70, 2.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.97(0.68, 2.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eBladder, kidney\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e1.74(1.05, 2.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.99(0.94, 2.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eBrain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e5.96(1.08, 33.0)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e8.42(1.32, 53.9)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eThyroid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e0.61(0.15, 2.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.80(0.20, 3.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.35166425470333%\" valign=\"top\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24891461649783%\" valign=\"top\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.971056439942114%\" valign=\"top\"\u003e\n \u003cp\u003e0.87(0.37, 2.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68162083936324%\" valign=\"top\"\u003e\n \u003cp\u003e0.83(0.36, 1.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRate\u003csup\u003e#\u003c/sup\u003e, incidence rate, per 1,000 person-years; Crude HR, relative hazard ratio;\u003c/p\u003e\n\u003cp\u003e\u0026dagger;Adjusting for age, sex, comorbidities and medications;\u003c/p\u003e\n\u003cp\u003e*p\u0026lt;0.05, **p\u0026lt;0.01\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3. Incidence and adjusted hazard ratio of colorectal cancer stratified by duration of colchicine therapy in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases in the propensity score matched cohort.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"621\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.375201288244767%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedication exposed\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.586151368760063%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerson-year\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.789049919484702%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.993558776167472%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted HR\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u0026dagger;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.375201288244767%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eColorectal cancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.586151368760063%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.789049919484702%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.993558776167472%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.375201288244767%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eColchicine \u003csup\u003e#\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.586151368760063%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.789049919484702%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.993558776167472%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.375201288244767%\" valign=\"top\"\u003e\n \u003cp\u003eNon-colchicine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e16026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.586151368760063%\" valign=\"top\"\u003e\n \u003cp\u003e123693\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.789049919484702%\" valign=\"top\"\u003e\n \u003cp\u003e1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.993558776167472%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.375201288244767%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;15 \u0026le; 20 days\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e8099\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.586151368760063%\" valign=\"top\"\u003e\n \u003cp\u003e61764\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.789049919484702%\" valign=\"top\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.993558776167472%\" valign=\"top\"\u003e\n \u003cp\u003e0.81(0.61, 1.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.375201288244767%\" valign=\"top\"\u003e\n \u003cp\u003e21-100 days \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e4036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.586151368760063%\" valign=\"top\"\u003e\n \u003cp\u003e30949\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.789049919484702%\" valign=\"top\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.993558776167472%\" valign=\"top\"\u003e\n \u003cp\u003e0.58(0.45, 0.99)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.375201288244767%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;100 days\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e3891\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.628019323671497%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.586151368760063%\" valign=\"top\"\u003e\n \u003cp\u003e30096\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.789049919484702%\" valign=\"top\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.993558776167472%\" valign=\"top\"\u003e\n \u003cp\u003e0.17(0.15, 0.66)**\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003e The cumulative use day are partitioned in to 3 segments by median, and third quartile\u003c/p\u003e\n\u003cp\u003eAdjusted HR\u0026dagger;: multivariable analysis including age, sex, comorbidities and medications;\u003c/p\u003e\n\u003cp\u003e*p\u0026lt;0.05, **p\u0026lt;0.01\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4.\u0026nbsp;Incidence and hazards ratio of colorectal cancer measured by age, sex, comorbidities and medications in the propensity-score-matched\u0026nbsp;cohorts\u0026nbsp;by Cox proportional hazard models with time-dependent exposure covariates\u0026nbsp;among\u0026nbsp;the musculoskeletal system and connective tissue and rheumatism-related diseases.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"598\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"70.40133779264214%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePropensity Score Matched\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.97324414715719%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eColchicine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.40468227424749%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N=\u003c/strong\u003e\u003cstrong\u003e16026\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.568561872909697%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N=\u003c/strong\u003e\u003cstrong\u003e16026\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRate\u003csup\u003e#\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRate\u003csup\u003e#\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted HR\u0026dagger; (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003eColorectal cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026le; 49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e0.27(0.12,0.83)**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e50-64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e1.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e0.79(0.40, 0.59)**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e65+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e2.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e0.88(0.36, 3.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e0.47(0.31, 0.66)**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.598662207357858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.367892976588628%\" valign=\"top\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e1.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.531772575250836%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.036789297658864%\" valign=\"top\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42809364548495%\" valign=\"top\"\u003e\n \u003cp\u003e0.61(0.55, 0.89)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRate\u003csup\u003e#\u003c/sup\u003e, incidence rate, per 1000 person-years; Adjusted HR\u0026dagger;: multivariable analysis including age, sex, comorbidities and medications;\u003c/p\u003e\n\u003cp\u003e*p\u0026lt;0.05; **p\u0026lt;0.01\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 5. Summary findings and speculations.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"8\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWithout stratification with age and sex.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eNLRP3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003csup\u003e\u0026yen;\u0026hearts;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eaHR\u003csup\u003e※※\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e-Protecting in chronic colitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eNLRP3 Dual Effect For Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eColchicine Modulate NLRP3 Effect For Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eHyperlipidemia\u003c/p\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003cp\u003eLiver cirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eDetection\u003c/p\u003e\n \u003cp\u003eBias\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eModulate aHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eeffect of\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1+2+3+4\u003c/p\u003e\n \u003cp\u003e=\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eColorectal cancer \u0026ndash;MD colitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e+/-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0/+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e▬\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"8\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStratification with Age and Sex.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eNLRP3 Effect for Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eTestosterone (+)\u003c/p\u003e\n \u003cp\u003eEstrogen (?) \u0026nbsp;\u003c/p\u003e\n \u003cp\u003eEffect For Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eHyperlipidemia\u003c/p\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003cp\u003eTobacco use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.715359828141784%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eColchicine Modulate NLRP3 Effect for Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.856068743286789%\" valign=\"top\"\u003e\n \u003cp\u003eaHR\u003csup\u003e※※\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eeffect of\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1+2+3+4\u003c/p\u003e\n \u003cp\u003e=\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003csup\u003e\u0026hearts;\u003c/sup\u003eColorectal cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.715359828141784%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.856068743286789%\" valign=\"top\"\u003e\n \u003cp\u003e▬\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.167919799498748%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.165413533834588%\" valign=\"top\"\u003e\n \u003cp\u003e▬\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;65-year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.167919799498748%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0/-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.165413533834588%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;65-year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.167919799498748%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.165413533834588%\" valign=\"top\"\u003e\n \u003cp\u003e▬\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.647887323943662%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.394366197183098%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"12.535211267605634%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"15.352112676056338%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.183098591549296%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"14.366197183098592%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"0.28169014084507044%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.23943661971831%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e+ were associated with enhancing the +aHR, -were associated with attenuating-aHR,0 were null effect on the aHR\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;aHR\u003csup\u003e※※\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eeffect of 1+2+3+4\u003c/p\u003e\n\u003cp\u003eMD,\u0026nbsp;the musculoskeletal system and connective tissue and rheumatism-related diseases\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026yen;\u003c/sup\u003e The colchicine users have received the higher frequency of medical services (N\u0026nbsp;≧\u0026nbsp;4) with the at least one procedure in relation to cancer diagnosis on these cancers than the colchicine nonusers (N=1)\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026hearts;\u0026nbsp;\u003c/sup\u003eIn colchicine users, the frequency of high up to 43.2% patients in brain cancer cohort have receved the brain\u0026ndash;related procedure for neurodegenerative diseases or head trauma. In contrast, in colorectal cancer cohort, only13% patients have received the colonscopy-related procedure. However, these colchicine users having the higher frequency of the examination of the cancers-related procedures than the colchicine non-users before the diagnosis of these cancers.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"colchicine, cancer risk, musculoskeletal system, connective tissue, rheumatism-related diseases","lastPublishedDoi":"10.21203/rs.3.rs-3789273/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3789273/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo determine the effect of colchicine on cancer risk in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases (MD).\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe retrospectively enrolled patients with the MD divided them into colchicine users (N\u0026thinsp;=\u0026thinsp;16,026) and colchicine nonusers (N\u0026thinsp;=\u0026thinsp;16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for tobacco use, anti-inflammatory drugs and immunosuppressant drugs.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eComparing the colchicine nonusers, only the colchicine users were associated with the lower incidence of the colorectal cancer ( (aHRs) (95% CI), 0.52 (0.49, 0.89)). Notably, the frequency of the medical services may inflate the aHR of brain tumor ((aHRs (95% CI), 8.42 (1.32, 53.9)). However, the aged\u0026thinsp;\u0026lt;\u0026thinsp;65 years adult having the colchicine users were associated with lower risk the colorectal cancer. Moreover, the colchicine\u0026thinsp;\u0026gt;\u0026thinsp;20 days use with the lower aHR for colorectal cancer.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study implied colchicine with an auxiliary role for protecting the colorectal cancer formation in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases.\u003c/p\u003e","manuscriptTitle":"Effect of colchicine on cancer risk in patients with the musculoskeletal system and connective tissue and rheumatism-related diseases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-02 19:09:21","doi":"10.21203/rs.3.rs-3789273/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-09T08:03:02+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-06T14:47:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"20fe9a17-566b-4bd2-9755-246833fa4910","date":"2024-02-02T07:33:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"d74bd030-1e5b-4c0d-ba6f-e1f331ab9e0f","date":"2024-01-28T08:05:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-12-28T16:47:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-12-28T04:43:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-12-26T11:30:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Medical Research","date":"2023-12-22T00:57:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cff482bc-e5c8-48d3-b44a-5f95c63aa216","owner":[],"postedDate":"January 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-04-10T06:32:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-02 19:09:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3789273","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3789273","identity":"rs-3789273","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}