Cross-country inequalities in global burden of gastrointestinal cancers: a slope and concentration index methods

Cross-country inequalities in global burden of gastrointestinal cancers: a slope and concentration index methods | 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 Cross-country inequalities in global burden of gastrointestinal cancers: a slope and concentration index methods Haoyun Zhou, Yongbo Wang, Fang Wang, Runtang Meng, Yong Yu, Su Han, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4826804/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose To explore cross-country inequalities in global disease burdens of colon and rectum cancer (CRC), esophageal cancer (EC) and gastric cancer (GC). Methods Data from the Global Burden of Diseases Study 2019 were analyzed to examine trends in disability-adjusted life-years (DALYs) for three cancers using Estimated Annual Percentage Change (EAPC) and Joinpoint analysis. Inequality in DALYs rates was assessed with the Slope Index of Inequality and the Concentration Index, based on the Socio-Demographic Index (SDI). Results From 1990 to 2019, age standardized DALYs rate of CRC decreased in high and high-middle SDI regions, with the EAPC values of -1.018 and − 0.161, but increased among low, low-middle and middle SDI regions (EAPC = 1.035, 0.926 and 0.406, respectively). The DALYs rates of EC and GC decreased in all SDI regions. For CRC, the slope index changed from 358.42 (95% confidence interval: 343.28 to 370.49) to 245.13 (217.47 to 271.24); from − 63.88 (-87.48 to -48.28) to -1.36 (-32.44 to 25.87) for EC; from 126.37 (101.97 to 146.47) to 58.04 (20.54 to 96.12) for GC. The concentration index for CRC moved from 29.56 (28.99 to 29.84) to 23.90 (23.19 to 24.26); from − 9.47 (-10.30 to -9.24) to -14.64 (-15.35 to -14.24) for EC; from 8.44 (7.85 to 8.72) to -6.42 (-7.65 to -6.12) for GC. Conclusion This study suggests strong heterogeneity in global DALYs for gastrointestinal cancers across different SDI regions. Higher SDI regions faced a greater burden of CRC, while the burdens of EC and GC were more prevalent in lower SDI regions. Health inequality Disability-adjusted life-years (DALYs) Gastrointestinal cancers Socio-Demographic Index (SDI) Figures Figure 1 Figure 2 Figure 3 Introduction Gastrointestinal cancers are one of the leading causes of death [ 1 ] . According to the predictions of global mortality and incidence of cancer [ 2 ] , new cases and deaths of gastrointestinal cancers are expected to increase significantly by 2040. Colon and rectum cancer (CRC) ranks the third among the most common cancers in the world, gastric cancer (GC) ranks sixth and esophageal cancer (EC) ranks the eighth. According to the report by World Health Organization (WHO) in 2020 [ 1 ] , there were 1,089,103 new cases and 768,793 deaths from GC worldwide, 604,100 new cases and 544,076 deaths from EC and a total of 1,880,725 new cases and 915,880 deaths from CRC. Gastrointestinal related cancers cause a huge burden of disease [ 3 ] . The geographical distribution of different gastrointestinal-related cancers varies greatly [ 4 – 7 ] . The incidence rate of CRC is high in Europe, North America, Australia, New Zealand, East Asia [ 4 ] . The incidence rate of GC is high in East Asia, Western Europe, South America [ 5 ] . The incidence rate of EC is high in East Asia, South Africa, East Africa and Northern Europe [ 6 – 7 ] . Gastrointestinal related cancers are an important obstacle to improving life expectancy. The levels of social and digital development vary in different regions. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) studies have become an important tool for major organizations and countries to provide epidemiological evidence and formulate relevant health policies. It can not only assess the incidence, prevalence, and mortality rate of diseases, but also assess the disease burden index including disability-adjusted life-years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). The GBD study covers 204 countries and territories and divides them into five levels based on the Socio-Demographic Index (SDI), including low, low-middle, middle, high-middle, and high SDI, allowing for the comparison of countries based on their social and demographic development levels [ 8 , 9 ] . The aim of this study was to analyze cross-country inequalities and the disease burden of three gastrointestinal cancers, including CRC, EC, and GC, over the period of 1990–2019. Cross-country inequality analysis was conducted using the method recommended by the WHO to explore whether there were inequalities related to the level of sociodemographic development in the DALYs burden of gastrointestinal cancers among countries or regions, and further to determine their extents and trends [ 10 ] . This study could provide epidemiological evidence for the global inequalities of gastrointestinal related cancers. Methods Data source The GBD 2019 study is a systematic effort to estimate incidence, prevalence, mortality, YLLs, YLDs, and DALYs for 369 causes of death and disability and 87 risk factors and groups of risk factors at the global level, regionally, and for 204 countries and territories. Data for CRC, EC, and GC each year were extracted from the GHDx section of the GBD Results Tool ( http://ghdx.healthdata.org/ ). The original data for CRC, EC, and GC were obtained from vital registrations, vital registration samples, verbal autopsies, hospital and claims data, literature data, and epidemiological survey data [ 3 ] . Age standardized rates of DALYs for CRC, EC, and GC were computed based on the global population reported by GBD [ 3 ] . We utilized the SDI to describe DALYs for CRC, EC, and GC across different regions. The SDI is closely related to social development status and population health outcomes according to per-capita income, total fertility rate, and average education level [ 8 ] . Description of the burden of disease and percent changes We used liner regression to evaluated annual percentage change (EAPC) of the age standardized DALYs rate of CRC, EC and GC over years. In the liner regression, the natural logarithm of the DALYs rate was used as the dependent variable and the year as the independent variable. A positive EAPC value represented an increase in the DALYs rate from 1990 to 2019, while a negative value indicated a decrease. We computed the EAPC by age and sex using the following general formula: y = α + βx + ε y = In (rate), x = calendar year EAPC = 100 × (e β -1) The joinpoints of percent changes in DALYs rate of the three cancers from 1990 to 2019 were calculated using the Joinpoint regression model. The annual percent changes and their statistically significant differences for each trend phases were calculated using the National Cancer Institute (NCI) Joinpoint regression program software (version 4.1.0; Statistical Research and Applications Branch, NCI). A positive value of annual percent change represented an increase in the DALYs rate over time, while a negative value indicated a decrease. Each SDI region was set up to three joinpoints to function. Cross-country inequality analysis The inequalities in the distribution of the cancer burden among countries were quantified through absolute inequality and relative inequality. The slope index and concentration index of inequality proposed by the WHO were used to evaluate absolute inequality and relative inequality. Their calculations involved weighting based on population size, quantifying inequality while also taking into account population size. The slope index of inequality was calculated by ranking a weighted sample of the entire population from the lowest SDI subgroup to the highest SDI subgroup. An appropriate model was then used to regress the DALYs rate with the midpoint of the SDI groups, and the predicted values for the two extreme SDI regions were calculated. The difference between these two predicted values generated the slope index of inequality. A positive value represented that the DALYs rate was more common in high SDI regions, while a negative value indicated the opposite. The indicator for measuring relative inequality was the concentration index. We used the concentration curve to illustrate the concentration index. The weighted samples of the entire population were sorted based on SDI from the most vulnerable subgroup to the most favorable subgroup (x-axis). The y-axis represented the cumulative fraction corresponding to the DALYs rate of each subgroup. The concentration curve was then drawn by connecting these points. The line connecting the bottom left corner to the top right corner was called the equality line. When the concentration curve was below the equality line, it indicated that the DALYs rate was concentrated in the high SDI subgroup. Conversely, when the concentration curve was above the equality line, it indicated that the DALYs rate was concentrated in the low SDI subgroup. All statistical analyses were conducted using R software (version 4.2.2), Stata software (version 17.0), and ArcMap (version 10.8). A p value of < 0.05 was considered to indicate statistically significant differences. Results The distribution and trend in age standardized DALYs rate of gastrointestinal cancers The age standardized DALYs rate of CRC varied remarkably worldwide in 2019 (Supplementary Fig. 1A). The age standardized DALYs rate of CRC decreased in high and high-middle SDI regions (Supplementary Table 1), with EAPC values of -1.018 and − 0.161, respectively, but increased in low, low-middle, and middle SDI regions during the study period of 1990–2019 (EAPC = 1.035, 0.926, and 0.406, respectively). Regionally, high and high-middle SDI regions had much higher DALYs rates due to CRC than other SDI regions (Supplementary Figs. 2A and 2B). The most significant DALYs rate occurred in the 95 + years age group (Supplementary Fig. 3A), and males appeared to demonstrate higher DALYs rates than females in most age groups. The age standardized DALYs rate of EC varied remarkably worldwide in 2019 (Supplementary Fig. 1B). The global age standardized DALYs rate of EC was 139.793 in 2019. From 1990 to 2019, EAPC values of EC were negative for all SDI regions (Supplementary Table 2). The age standardized DALYs rate in the middle SDI region decreased significantly (Supplementary Fig. 2C). EC had a much higher burden in middle and high-middle SDI regions than in other SDI regions (Supplementary Fig. 2C). The most significant DALYs rate occurred in the 70–74 years age group, and the DALYs rate of EC in males was higher than in females across all age groups (Supplementary Fig. 3B). The age standardized DALYs rate of GC varied remarkably worldwide in 2019 (Supplementary Fig. 1C). Regionally, the age standardized DALYs rate of GC in the middle SDI region was the highest in 2019, with a value of 323.393. EAPC values of GC were negative for all SDI regions (Supplementary Table 3). The age standardized DALYs rate decreased in all SDI regions (Supplementary Fig. 2E). The crude DALYs rate also showed a general downward trend (Supplementary Fig. 2F). Compared to other SDI regions, the high-middle and middle SDI regions had significantly higher age standardized DALYs rates due to GC (Supplementary Fig. 2E). The most significant DALYs rate occurred in the 70–74 years age group, and in most age groups, the DALYs rate in males was higher than in females (Supplementary Fig. 3C). Cross-country inequality of cancers Colon and rectum cancer It was observed that countries with higher SDI had a higher burden in absolute and relative inequalities in 1990 and 2019 (Fig. 1 ). As shown by the slope index of inequality, the difference in DALYs rate between the highest and lowest SDI countries decreased from 358.42 (95% confidence interval [CI]: 343.28 to 370.49) in 1990 to 245.13 (95% CI: 217.47 to 271.24) in 2019. The concentration index was 29.56 (95% CI: 28.99 to 29.84) in 1990 and 23.90 (95% CI: 23.19 to 24.26) in 2019. Furthermore, the slope index and concentration index of inequalities showed a general downward trend from 1990 to 2019. Esophageal cancer It was observed that countries with lower SDI had a higher burden in absolute and relative inequalities in 1990 and 2019 (Fig. 2 ). As shown by the slope index of inequality, the difference in DALYs rate between the highest and lowest SDI countries changed from − 63.88 (95% CI: -87.48 to -48.28) in 1990 to -1.36 (95% CI: -32.44 to 25.87) in 2019. The concentration index was − 9.47 (95% CI: -10.30 to -9.24) in 1990 and − 14.64 (95% CI: -15.35 to -14.24) in 2019. Moreover, the absolute value of the slope index of inequality showed an upward trend from 1990 to 2005, becoming positive in 2002, decreasing from 2005 to 2019, and becoming negative in 2017. The concentration index of inequality showed a general downward trend from 1990 to 2019. Gastric cancer It was observed that countries with higher SDI had a higher burden in absolute inequality in 1990 and 2019 (Fig. 3 ). The countries with higher SDI had a higher burden in relative inequality in 1990, but in 2019, the countries with higher SDI had a lower burden in relative inequality. As shown by the slope index of inequality, the difference in DALYs rate between the highest and lowest SDI countries decreased from 126.37 (95% CI: 101.97 to 146.47) in 1990 to 58.04 (95% CI: 20.54 to 96.12) in 2019. The concentration index was 8.44 (95% CI: 7.85 to 8.72) in 1990 and − 6.42 (95% CI: -7.65 to -6.12) in 2019. In addition, the slope index of inequality showed a trend of first decreasing, then increasing, and finally decreasing, while the absolute value of the concentration index of inequality showed a trend of first decreasing and then increasing. Overall, in 2019, from the perspective of the slope index of inequality, high SDI countries bore relatively more of the burden caused by CRC and GC, while low SDI countries bore more of the burden caused by EC. From the perspective of the concentration index, high SDI countries bore relatively more of the burden caused by CRC, while low SDI countries bore more of the burden caused by EC and GC. Discussion In this study, we described the disease burden and age, gender, and geographical distribution of CRC, EC, and GC, and analyzed the cross-country inequalities in the disease burden of these three cancers. The great advantage of our research is that it shows the cross-country inequalities in different SDI levels related to CRC, EC, and GC. Our article could provide epidemiological evidence for the global inequalities of gastrointestinal related cancers. Our research showed that 2004 was a significant joint point for the three types of cancer, with the age standardized DALYs rates of these diseases showing a downward trend. We speculated that this might be related to the improved medical standards. As reported, some molecular targeted therapies can focus on specific molecules in gastrointestinal cancer cells [ 13 , 14 ] . For example, Bevacizumab was approved in February 2004 for the treatment of CRC [ 15 , 16 ] . The results of this study showed that compared to low SDI countries, high SDI countries bore a greater burden of disease related to CRC. The burden of CRC varied greatly, depending on geographical region, gender, age and socio-economic status [ 17 ] . Common sense believed that compared to high SDI countries, low SDI countries would suffer a greater burden of CRC. However, the results of our study indicate that countries with high SDI actually had disproportionately a higher disease burden. This might be because the lifestyle of people in countries with high SDI increased the incidence rate of cancer. Related studies have shown that individual factors such as overweight or obesity, other disease burdens, and lifestyle habits such as consuming processed meat and alcohol could increase the risk of CRC [ 18 – 20 ] . Many risk factors for CRC, such as sedentary lifestyle and dietary patterns in developed Western countries, are common behaviors among people in high SDI countries [ 21 ] . The study by Hongmeizhu et al. suggested that areas with high SDI should pay more attention to CRC [ 22 ] . A Chinese study also showed that the age standardized incidence rate of CRC was positively correlated with Gross Domestic Product (GDP) per capita. A study on the global disease burden of CRC had concluded that the incidence rate of CRC in more developed regions was 2.5 times that in less developed regions, and the mortality rate was twice that in less developed regions [ 23 , 24 ] . Our study concluded that in low SDI regions, there is a relatively greater burden of disease caused by EC. This is similar to the research results of Yang Zhixun et al., who found that the incidence rate and mortality of EC were higher in middle and low GDP regions than in high GDP regions [ 23 ] . Due to the lack of specific symptoms of early EC, most tumors are diagnosed in the late stage and rapidly progressed to the late stage when treatment options are limited and cure is impossible. In high-income environments, only about a quarter of EC patients survive within 5 years after diagnosis [ 25 ] . Therefore, disease prevention is particularly important. Risk factors for developing EC included smoking and alcohol abuse [ 26 – 29 ] , drinking hot tea [ 30 , 31 ] , poor oral health [ 32 ] , and low intake of fresh fruits and vegetables [ 33 , 34 ] . Relevant departments or governments can develop prevention strategies to reduce the risk of disease occurrence, such as discouraging smoking and alcohol consumption, promoting dental care, encouraging the consumption of fruits and vegetables, and incorporating foods with high antioxidant properties into local diets. The results of our study indicated that the slope of inequality related to GC was positive, suggesting that high SDI countries bore more of the burden caused by GC. However, from the perspective of the concentration index, starting from 2009, the concentration index became negative, indicating that low SDI countries bore more of the burden caused by GC. This finding was inconsistent with the results of absolute inequality. The reason for this discrepancy is that the slope index evaluating absolute inequality only represents the difference in predicted values between the highest and lowest SDI levels, while the concentration index evaluating relative inequality considers all SDI subgroups. Relevant explanations can be found in this book published by the WHO [ 10 ] . For GC, low SDI regions have borne a greater burden of disease since 2009. On a global scale, many studies have also reached similar conclusions [ 22 , 23 , 25 ] . The diagnosis and treatment costs of GC are high, and we should adhere to the principle of prevention first. Research has shown that taking vitamin D supplements was an effective way to reduce cancer risk [ 36 ] . Studies in high-risk areas such as Japan and Korea found that screening also leads to a significant reduction in GC related mortality [ 37 , 38 ] . Several limitations should be noted in our study. GBD data typically use complex models to estimate indicators based on assumptions and data imputations [ 39 ] . These assumptions and imputation may affect the accuracy of the data. In economically disadvantaged regions, there might be some missing data. In addition, the disease burden in low SDI areas might be underestimated due to poor economic conditions leading to incomplete disease screening and possible data loss. Conclusion In summary, a decreasing long-term trend was observed in the age standardized DALYs rate of CRC in high and high-middle SDI regions, while an increasing trend was observed among low, low-middle, and middle SDI regions during the period of 1990–2019. The DALYs rates of EC and GC showed a decreasing trend in all SDI regions. This study indicated that strong heterogeneity in the regional distribution of global DALYs rate for CRC, EC and GC. Countries with higher levels of social and demographic development bore a higher burden of CRC. EC and GC now pose a greater disease burden in low SDI areas than in high SDI areas. This study provided epidemiological evidence for global inequalities in gastrointestinal related cancers. We suggest further research should be focused on the cross-country inequalities in gastrointestinal cancers, and it is important to establish effective prevention and treatment plans to reduce the burden caused by gastrointestinal cancers. Abbreviations CRC: colon and rectum cancer; EC: esophageal cancer; GC: gastric cancer; EAPC: Estimated annual percentage change; DALYs: disability-adjusted life-years; SDI: Socio-Demographic Index; CI: confidence interval; WHO: World Health Organization; GBD: Global Burden of Diseases, Injuries, and Risk Factors; YLDs: years of life lived with disability; YLLs: years of life lost; NCI: National Cancer Institute; GDP: Gross Domestic Product. Declarations Competing interests: The authors declare that they have no conflicts of interest. Acknowledgements: We appreciate the works by the 2019 Global Burden of Disease study collaborators. This work was funded by the National Natural Science Foundation of China [grant number 82173626], and the Health Commission of Hubei Province Scientific Research Major Project [grant number WJ2019H304]. Ethics approval and informed consent The datasets analyzed during the current study are published and available in the [Global Burden of Disease Database] repository. Thus, ethics approval and patient consent to participate were not applicable in this study. Consent for publication Figure, table and other information are confirmed and approved for publication Data availability The datasets analyzed in the current study are available in the GBD repository, https://vizhub.healthdata.org/gbd-results. Authors' contributions X.L. conceived of the study and participated in its design and coordination. 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Supplementary Files SupplementaryFigure1A.pdf SupplementaryFigure1B.pdf SupplementaryFigure1C.pdf SupplementaryFigure2A.pdf SupplementaryFigure2B.pdf SupplementaryFigure2C.pdf SupplementaryFigure2D.pdf SupplementaryFigure2E.pdf SupplementaryFigure2F.pdf SupplementaryFigure3A.jpg SupplementaryFigure3B.jpg SupplementaryFigure3C.jpg Supplementarytables.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 01 Nov, 2024 Reviews received at journal 30 Oct, 2024 Reviewers agreed at journal 03 Oct, 2024 Reviews received at journal 02 Sep, 2024 Reviewers agreed at journal 26 Aug, 2024 Reviewers invited by journal 09 Aug, 2024 Editor assigned by journal 07 Aug, 2024 Submission checks completed at journal 06 Aug, 2024 First submitted to journal 30 Jul, 2024 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-4826804","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":347017948,"identity":"66b6004c-a5aa-43bd-aad2-5676c8a35205","order_by":0,"name":"Haoyun Zhou","email":"","orcid":"","institution":"Jiangnan University","correspondingAuthor":false,"prefix":"","firstName":"Haoyun","middleName":"","lastName":"Zhou","suffix":""},{"id":347017949,"identity":"a7e798c3-0b34-4640-846f-8f80bd33671e","order_by":1,"name":"Yongbo Wang","email":"","orcid":"","institution":"Zhongnan Hospital of Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Yongbo","middleName":"","lastName":"Wang","suffix":""},{"id":347017950,"identity":"413269ab-672d-42ab-b6b3-d423c77112da","order_by":2,"name":"Fang Wang","email":"","orcid":"","institution":"Xuzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Wang","suffix":""},{"id":347017952,"identity":"c95e6b83-bf1f-47ac-ab95-b5ddb6ca2240","order_by":3,"name":"Runtang Meng","email":"","orcid":"","institution":"Hangzhou Normal University","correspondingAuthor":false,"prefix":"","firstName":"Runtang","middleName":"","lastName":"Meng","suffix":""},{"id":347017954,"identity":"278371e8-0cf5-4476-b1ba-b6422eaf7284","order_by":4,"name":"Yong Yu","email":"","orcid":"","institution":"Hubei University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"","lastName":"Yu","suffix":""},{"id":347017956,"identity":"a92a0dd2-5a29-4422-a90a-61ac202bb2ed","order_by":5,"name":"Su Han","email":"","orcid":"","institution":"Jiangnan University","correspondingAuthor":false,"prefix":"","firstName":"Su","middleName":"","lastName":"Han","suffix":""},{"id":347017959,"identity":"142caefa-04f7-4f78-b33e-6c7366f94d41","order_by":6,"name":"Yu Zhang","email":"","orcid":"","institution":"Jiangnan University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Zhang","suffix":""},{"id":347017961,"identity":"47febb41-fd7d-4a71-b8f4-20869e7643a2","order_by":7,"name":"Yu Wu","email":"","orcid":"","institution":"Jiangnan University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Wu","suffix":""},{"id":347017963,"identity":"3a42ba16-5ea7-4f92-88fc-f0f2a5411782","order_by":8,"name":"Xiaoxue Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYBACPmYQaSAhx89wsAEuKoFPCxtYS4WFsWQD0VrA5JmKxA0HkETxa2HnMZPmbZNI3HzwcOPngl935M0ZmA/e5mGwy8PtMB5jw5ltEsbbDhxslp7Z98xwZwNbsjUPQ3IxHi2GDz62ScgCtTRI8/YcZtxwAGgvD8OBxAbcWgwOJLZJMG5uONj8G6jFfsMB/m+EtBg++HBGQnEDw8E2aZ4fh4HhwMNGQAtbseGMCgljiQMH26x5Gw4nbzjMZmw5xyAZpxZ+/sPbpHkM6uT4Zxx/fJvnz2HbDcebH954U2GHUwsCSBxgYGBsAzIg6YGgepB9IFP/EKNyFIyCUTAKRhoAAAa0V0Q7HKU4AAAAAElFTkSuQmCC","orcid":"","institution":"Jiangnan University","correspondingAuthor":true,"prefix":"","firstName":"Xiaoxue","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-07-30 08:05:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4826804/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4826804/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63633719,"identity":"aa3ed17a-ac06-4058-8669-9d0588216399","added_by":"auto","created_at":"2024-08-30 11:17:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2444153,"visible":true,"origin":"","legend":"\u003cp\u003eHealth inequality regression curves and concentration curves for the DALYs of CRC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations: \u003c/strong\u003eDALYs, disability-adjusted life-years; CI, confidence interval; CRC, colon and rectum cancer.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4826804/v1/e13a63354a84985bacf38b18.png"},{"id":63634265,"identity":"e1937b18-fc11-40cd-97c6-e351e40d9d25","added_by":"auto","created_at":"2024-08-30 11:25:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":553872,"visible":true,"origin":"","legend":"\u003cp\u003eHealth inequality regression curves and concentration curves for the DALYs of EC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations: \u003c/strong\u003eDALYs, disability-adjusted life-years; CI, confidence interval; EC, esophageal cancer.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4826804/v1/b4345c7142356a2601666d74.png"},{"id":63633718,"identity":"8da2f611-9567-4bea-a661-f6233bc12b8d","added_by":"auto","created_at":"2024-08-30 11:17:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2350207,"visible":true,"origin":"","legend":"\u003cp\u003eHealth inequality regression curves and concentration curves for the DALYs of GC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations: \u003c/strong\u003eDALYs, disability-adjusted life-years; CI, confidence interval; GC, gastric cancer.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4826804/v1/581ce04368dced132e836643.png"},{"id":63634655,"identity":"36a8e6c7-f143-454c-9619-d6a570f61a9b","added_by":"auto","created_at":"2024-08-30 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11:25:35","extension":"jpg","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":185100,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure3A.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4826804/v1/199cf06192c7032a9856c57e.jpg"},{"id":63633733,"identity":"540d26b5-318b-414c-8fa3-dcbfe7d7c47a","added_by":"auto","created_at":"2024-08-30 11:17:35","extension":"jpg","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":182147,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure3B.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4826804/v1/a6c092edf5ea2d27679f61a5.jpg"},{"id":63633727,"identity":"20d163d5-0596-45e9-b528-abfb158b8898","added_by":"auto","created_at":"2024-08-30 11:17:34","extension":"jpg","order_by":13,"title":"","display":"","copyAsset":false,"role":"supplement","size":181297,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure3C.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4826804/v1/c781a0b3b523ef938b74aee8.jpg"},{"id":63634268,"identity":"ad963942-a5ab-4db4-a691-ca701ebf172a","added_by":"auto","created_at":"2024-08-30 11:25:34","extension":"docx","order_by":14,"title":"","display":"","copyAsset":false,"role":"supplement","size":26544,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytables.docx","url":"https://assets-eu.researchsquare.com/files/rs-4826804/v1/f5672d40c34441d4893ea24f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cross-country inequalities in global burden of gastrointestinal cancers: a slope and concentration index methods","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGastrointestinal cancers are one of the leading causes of death\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. According to the predictions of global mortality and incidence of cancer\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, new cases and deaths of gastrointestinal cancers are expected to increase significantly by 2040. Colon and rectum cancer (CRC) ranks the third among the most common cancers in the world, gastric cancer (GC) ranks sixth and esophageal cancer (EC) ranks the eighth. According to the report by World Health Organization (WHO) in 2020\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, there were 1,089,103 new cases and 768,793 deaths from GC worldwide, 604,100 new cases and 544,076 deaths from EC and a total of 1,880,725 new cases and 915,880 deaths from CRC. Gastrointestinal related cancers cause a huge burden of disease\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe geographical distribution of different gastrointestinal-related cancers varies greatly\u003csup\u003e[\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. The incidence rate of CRC is high in Europe, North America, Australia, New Zealand, East Asia\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The incidence rate of GC is high in East Asia, Western Europe, South America\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. The incidence rate of EC is high in East Asia, South Africa, East Africa and Northern Europe\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Gastrointestinal related cancers are an important obstacle to improving life expectancy. The levels of social and digital development vary in different regions. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) studies have become an important tool for major organizations and countries to provide epidemiological evidence and formulate relevant health policies. It can not only assess the incidence, prevalence, and mortality rate of diseases, but also assess the disease burden index including disability-adjusted life-years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). The GBD study covers 204 countries and territories and divides them into five levels based on the Socio-Demographic Index (SDI), including low, low-middle, middle, high-middle, and high SDI, allowing for the comparison of countries based on their social and demographic development levels\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe aim of this study was to analyze cross-country inequalities and the disease burden of three gastrointestinal cancers, including CRC, EC, and GC, over the period of 1990\u0026ndash;2019. Cross-country inequality analysis was conducted using the method recommended by the WHO to explore whether there were inequalities related to the level of sociodemographic development in the DALYs burden of gastrointestinal cancers among countries or regions, and further to determine their extents and trends\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. This study could provide epidemiological evidence for the global inequalities of gastrointestinal related cancers.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData source\u003c/h2\u003e \u003cp\u003eThe GBD 2019 study is a systematic effort to estimate incidence, prevalence, mortality, YLLs, YLDs, and DALYs for 369 causes of death and disability and 87 risk factors and groups of risk factors at the global level, regionally, and for 204 countries and territories. Data for CRC, EC, and GC each year were extracted from the GHDx section of the GBD Results Tool (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://ghdx.healthdata.org/\u003c/span\u003e\u003cspan address=\"http://ghdx.healthdata.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The original data for CRC, EC, and GC were obtained from vital registrations, vital registration samples, verbal autopsies, hospital and claims data, literature data, and epidemiological survey data\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Age standardized rates of DALYs for CRC, EC, and GC were computed based on the global population reported by GBD\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. We utilized the SDI to describe DALYs for CRC, EC, and GC across different regions. The SDI is closely related to social development status and population health outcomes according to per-capita income, total fertility rate, and average education level\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDescription of the burden of disease and percent changes\u003c/h2\u003e \u003cp\u003eWe used liner regression to evaluated annual percentage change (EAPC) of the age standardized DALYs rate of CRC, EC and GC over years. In the liner regression, the natural logarithm of the DALYs rate was used as the dependent variable and the year as the independent variable. A positive EAPC value represented an increase in the DALYs rate from 1990 to 2019, while a negative value indicated a decrease. We computed the EAPC by age and sex using the following general formula:\u003c/p\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;α\u0026thinsp;+\u0026thinsp;βx\u0026thinsp;+\u0026thinsp;ε\u003c/p\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;In (rate), x\u0026thinsp;=\u0026thinsp;calendar year\u003c/p\u003e \u003cp\u003eEAPC\u0026thinsp;=\u0026thinsp;100 \u0026times; (e\u003csup\u003eβ\u003c/sup\u003e-1)\u003c/p\u003e \u003cp\u003eThe joinpoints of percent changes in DALYs rate of the three cancers from 1990 to 2019 were calculated using the Joinpoint regression model. The annual percent changes and their statistically significant differences for each trend phases were calculated using the National Cancer Institute (NCI) Joinpoint regression program software (version 4.1.0; Statistical Research and Applications Branch, NCI). A positive value of annual percent change represented an increase in the DALYs rate over time, while a negative value indicated a decrease. Each SDI region was set up to three joinpoints to function.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCross-country inequality analysis\u003c/h2\u003e \u003cp\u003eThe inequalities in the distribution of the cancer burden among countries were quantified through absolute inequality and relative inequality. The slope index and concentration index of inequality proposed by the WHO were used to evaluate absolute inequality and relative inequality. Their calculations involved weighting based on population size, quantifying inequality while also taking into account population size.\u003c/p\u003e \u003cp\u003eThe slope index of inequality was calculated by ranking a weighted sample of the entire population from the lowest SDI subgroup to the highest SDI subgroup. An appropriate model was then used to regress the DALYs rate with the midpoint of the SDI groups, and the predicted values for the two extreme SDI regions were calculated. The difference between these two predicted values generated the slope index of inequality. A positive value represented that the DALYs rate was more common in high SDI regions, while a negative value indicated the opposite.\u003c/p\u003e \u003cp\u003eThe indicator for measuring relative inequality was the concentration index. We used the concentration curve to illustrate the concentration index. The weighted samples of the entire population were sorted based on SDI from the most vulnerable subgroup to the most favorable subgroup (x-axis). The y-axis represented the cumulative fraction corresponding to the DALYs rate of each subgroup. The concentration curve was then drawn by connecting these points. The line connecting the bottom left corner to the top right corner was called the equality line. When the concentration curve was below the equality line, it indicated that the DALYs rate was concentrated in the high SDI subgroup. Conversely, when the concentration curve was above the equality line, it indicated that the DALYs rate was concentrated in the low SDI subgroup.\u003c/p\u003e \u003cp\u003eAll statistical analyses were conducted using R software (version 4.2.2), Stata software (version 17.0), and ArcMap (version 10.8). A p value of \u0026lt;\u0026thinsp;0.05 was considered to indicate statistically significant differences.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eThe distribution and trend in age standardized DALYs rate of gastrointestinal cancers\u003c/h2\u003e \u003cp\u003eThe age standardized DALYs rate of CRC varied remarkably worldwide in 2019 (Supplementary Fig.\u0026nbsp;1A). The age standardized DALYs rate of CRC decreased in high and high-middle SDI regions (Supplementary Table\u0026nbsp;1), with EAPC values of -1.018 and \u0026minus;\u0026thinsp;0.161, respectively, but increased in low, low-middle, and middle SDI regions during the study period of 1990\u0026ndash;2019 (EAPC\u0026thinsp;=\u0026thinsp;1.035, 0.926, and 0.406, respectively). Regionally, high and high-middle SDI regions had much higher DALYs rates due to CRC than other SDI regions (Supplementary Figs.\u0026nbsp;2A and 2B). The most significant DALYs rate occurred in the 95\u0026thinsp;+\u0026thinsp;years age group (Supplementary Fig.\u0026nbsp;3A), and males appeared to demonstrate higher DALYs rates than females in most age groups.\u003c/p\u003e \u003cp\u003eThe age standardized DALYs rate of EC varied remarkably worldwide in 2019 (Supplementary Fig.\u0026nbsp;1B). The global age standardized DALYs rate of EC was 139.793 in 2019. From 1990 to 2019, EAPC values of EC were negative for all SDI regions (Supplementary Table\u0026nbsp;2). The age standardized DALYs rate in the middle SDI region decreased significantly (Supplementary Fig.\u0026nbsp;2C). EC had a much higher burden in middle and high-middle SDI regions than in other SDI regions (Supplementary Fig.\u0026nbsp;2C). The most significant DALYs rate occurred in the 70\u0026ndash;74 years age group, and the DALYs rate of EC in males was higher than in females across all age groups (Supplementary Fig.\u0026nbsp;3B).\u003c/p\u003e \u003cp\u003eThe age standardized DALYs rate of GC varied remarkably worldwide in 2019 (Supplementary Fig.\u0026nbsp;1C). Regionally, the age standardized DALYs rate of GC in the middle SDI region was the highest in 2019, with a value of 323.393. EAPC values of GC were negative for all SDI regions (Supplementary Table\u0026nbsp;3). The age standardized DALYs rate decreased in all SDI regions (Supplementary Fig.\u0026nbsp;2E). The crude DALYs rate also showed a general downward trend (Supplementary Fig.\u0026nbsp;2F). Compared to other SDI regions, the high-middle and middle SDI regions had significantly higher age standardized DALYs rates due to GC (Supplementary Fig.\u0026nbsp;2E). The most significant DALYs rate occurred in the 70\u0026ndash;74 years age group, and in most age groups, the DALYs rate in males was higher than in females (Supplementary Fig.\u0026nbsp;3C).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCross-country inequality of cancers\u003c/h2\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eColon and rectum cancer\u003c/h2\u003e \u003cp\u003eIt was observed that countries with higher SDI had a higher burden in absolute and relative inequalities in 1990 and 2019 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). As shown by the slope index of inequality, the difference in DALYs rate between the highest and lowest SDI countries decreased from 358.42 (95% confidence interval [CI]: 343.28 to 370.49) in 1990 to 245.13 (95% CI: 217.47 to 271.24) in 2019. The concentration index was 29.56 (95% CI: 28.99 to 29.84) in 1990 and 23.90 (95% CI: 23.19 to 24.26) in 2019. Furthermore, the slope index and concentration index of inequalities showed a general downward trend from 1990 to 2019.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eEsophageal cancer\u003c/h2\u003e \u003cp\u003eIt was observed that countries with lower SDI had a higher burden in absolute and relative inequalities in 1990 and 2019 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). As shown by the slope index of inequality, the difference in DALYs rate between the highest and lowest SDI countries changed from \u0026minus;\u0026thinsp;63.88 (95% CI: -87.48 to -48.28) in 1990 to -1.36 (95% CI: -32.44 to 25.87) in 2019. The concentration index was \u0026minus;\u0026thinsp;9.47 (95% CI: -10.30 to -9.24) in 1990 and \u0026minus;\u0026thinsp;14.64 (95% CI: -15.35 to -14.24) in 2019. Moreover, the absolute value of the slope index of inequality showed an upward trend from 1990 to 2005, becoming positive in 2002, decreasing from 2005 to 2019, and becoming negative in 2017. The concentration index of inequality showed a general downward trend from 1990 to 2019.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eGastric cancer\u003c/h2\u003e \u003cp\u003eIt was observed that countries with higher SDI had a higher burden in absolute inequality in 1990 and 2019 (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The countries with higher SDI had a higher burden in relative inequality in 1990, but in 2019, the countries with higher SDI had a lower burden in relative inequality. As shown by the slope index of inequality, the difference in DALYs rate between the highest and lowest SDI countries decreased from 126.37 (95% CI: 101.97 to 146.47) in 1990 to 58.04 (95% CI: 20.54 to 96.12) in 2019. The concentration index was 8.44 (95% CI: 7.85 to 8.72) in 1990 and \u0026minus;\u0026thinsp;6.42 (95% CI: -7.65 to -6.12) in 2019. In addition, the slope index of inequality showed a trend of first decreasing, then increasing, and finally decreasing, while the absolute value of the concentration index of inequality showed a trend of first decreasing and then increasing.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOverall, in 2019, from the perspective of the slope index of inequality, high SDI countries bore relatively more of the burden caused by CRC and GC, while low SDI countries bore more of the burden caused by EC. From the perspective of the concentration index, high SDI countries bore relatively more of the burden caused by CRC, while low SDI countries bore more of the burden caused by EC and GC.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we described the disease burden and age, gender, and geographical distribution of CRC, EC, and GC, and analyzed the cross-country inequalities in the disease burden of these three cancers. The great advantage of our research is that it shows the cross-country inequalities in different SDI levels related to CRC, EC, and GC. Our article could provide epidemiological evidence for the global inequalities of gastrointestinal related cancers.\u003c/p\u003e \u003cp\u003eOur research showed that 2004 was a significant joint point for the three types of cancer, with the age standardized DALYs rates of these diseases showing a downward trend. We speculated that this might be related to the improved medical standards. As reported, some molecular targeted therapies can focus on specific molecules in gastrointestinal cancer cells\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. For example, Bevacizumab was approved in February 2004 for the treatment of CRC\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe results of this study showed that compared to low SDI countries, high SDI countries bore a greater burden of disease related to CRC. The burden of CRC varied greatly, depending on geographical region, gender, age and socio-economic status\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. Common sense believed that compared to high SDI countries, low SDI countries would suffer a greater burden of CRC. However, the results of our study indicate that countries with high SDI actually had disproportionately a higher disease burden. This might be because the lifestyle of people in countries with high SDI increased the incidence rate of cancer. Related studies have shown that individual factors such as overweight or obesity, other disease burdens, and lifestyle habits such as consuming processed meat and alcohol could increase the risk of CRC\u003csup\u003e[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Many risk factors for CRC, such as sedentary lifestyle and dietary patterns in developed Western countries, are common behaviors among people in high SDI countries\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. The study by Hongmeizhu et al. suggested that areas with high SDI should pay more attention to CRC\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. A Chinese study also showed that the age standardized incidence rate of CRC was positively correlated with Gross Domestic Product (GDP) per capita. A study on the global disease burden of CRC had concluded that the incidence rate of CRC in more developed regions was 2.5 times that in less developed regions, and the mortality rate was twice that in less developed regions\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur study concluded that in low SDI regions, there is a relatively greater burden of disease caused by EC. This is similar to the research results of Yang Zhixun et al., who found that the incidence rate and mortality of EC were higher in middle and low GDP regions than in high GDP regions\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDue to the lack of specific symptoms of early EC, most tumors are diagnosed in the late stage and rapidly progressed to the late stage when treatment options are limited and cure is impossible. In high-income environments, only about a quarter of EC patients survive within 5 years after diagnosis\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Therefore, disease prevention is particularly important. Risk factors for developing EC included smoking and alcohol abuse\u003csup\u003e[\u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e, drinking hot tea\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e, poor oral health\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e, and low intake of fresh fruits and vegetables\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. Relevant departments or governments can develop prevention strategies to reduce the risk of disease occurrence, such as discouraging smoking and alcohol consumption, promoting dental care, encouraging the consumption of fruits and vegetables, and incorporating foods with high antioxidant properties into local diets.\u003c/p\u003e \u003cp\u003eThe results of our study indicated that the slope of inequality related to GC was positive, suggesting that high SDI countries bore more of the burden caused by GC. However, from the perspective of the concentration index, starting from 2009, the concentration index became negative, indicating that low SDI countries bore more of the burden caused by GC. This finding was inconsistent with the results of absolute inequality. The reason for this discrepancy is that the slope index evaluating absolute inequality only represents the difference in predicted values between the highest and lowest SDI levels, while the concentration index evaluating relative inequality considers all SDI subgroups. Relevant explanations can be found in this book published by the WHO\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFor GC, low SDI regions have borne a greater burden of disease since 2009. On a global scale, many studies have also reached similar conclusions\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. The diagnosis and treatment costs of GC are high, and we should adhere to the principle of prevention first. Research has shown that taking vitamin D supplements was an effective way to reduce cancer risk\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e. Studies in high-risk areas such as Japan and Korea found that screening also leads to a significant reduction in GC related mortality\u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSeveral limitations should be noted in our study. GBD data typically use complex models to estimate indicators based on assumptions and data imputations\u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. These assumptions and imputation may affect the accuracy of the data. In economically disadvantaged regions, there might be some missing data. In addition, the disease burden in low SDI areas might be underestimated due to poor economic conditions leading to incomplete disease screening and possible data loss.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, a decreasing long-term trend was observed in the age standardized DALYs rate of CRC in high and high-middle SDI regions, while an increasing trend was observed among low, low-middle, and middle SDI regions during the period of 1990\u0026ndash;2019. The DALYs rates of EC and GC showed a decreasing trend in all SDI regions. This study indicated that strong heterogeneity in the regional distribution of global DALYs rate for CRC, EC and GC. Countries with higher levels of social and demographic development bore a higher burden of CRC. EC and GC now pose a greater disease burden in low SDI areas than in high SDI areas. This study provided epidemiological evidence for global inequalities in gastrointestinal related cancers. We suggest further research should be focused on the cross-country inequalities in gastrointestinal cancers, and it is important to establish effective prevention and treatment plans to reduce the burden caused by gastrointestinal cancers.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCRC: colon and rectum cancer; EC: esophageal cancer; GC: gastric cancer;\u003c/p\u003e\n\u003cp\u003eEAPC: Estimated annual percentage change; DALYs: disability-adjusted life-years;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSDI: Socio-Demographic Index; CI: confidence interval; WHO: World Health Organization; GBD: Global Burden of Diseases, Injuries, and Risk Factors; YLDs: years of life lived with disability; YLLs: years of life lost; NCI: National Cancer Institute; GDP: Gross Domestic Product.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e We appreciate the works by the 2019 Global Burden of Disease study collaborators. This work was funded by the National Natural Science Foundation of China [grant number 82173626], and the Health Commission of Hubei Province Scientific Research Major Project [grant number WJ2019H304].\u003c/p\u003e\n\u003cp\u003eEthics approval and informed consent\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are published and available in the [Global Burden of Disease Database] repository. Thus, ethics approval and patient consent to participate were not applicable in this study.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFigure, table and other information are confirmed and approved for publication\u003c/p\u003e\n\u003cp\u003eData availability\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed in the current study are available in the GBD repository, https://vizhub.healthdata.org/gbd-results.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eX.L. conceived of the study and participated in its design and coordination. H.Z. and Y.W. led the data collection and analysis, wrote the original draft and oversaw the editing of the final manuscript. All authors contributed to the drafting and revision of the article and read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. \u003cem\u003eCA Cancer J Clin\u003c/em\u003e. 2021;71(3):209-249. doi:10.3322/caac.21660\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Cancer Tomorrow. Available: https://gco.iarc.fr/tomorrow/en. Accessed: 10 November 2023. \u003c/li\u003e\n\u003cli\u003eGBD 2019 Diseases and Injuries Collaborators. 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Nat Rev Cancer. 2014 May;14(5):342-57.\u003c/li\u003e\n\u003cli\u003eHamashima C, Ogoshi K, Okamoto M, Shabana M, Kishimoto T, Fukao A. A community-based, case-control study evaluating mortality reduction from gastric cancer by endoscopic screening in Japan. \u003cem\u003ePLoS One\u003c/em\u003e. 2013;8(11):e79088. Published 2013 Nov 13. doi:10.1371/journal.pone.0079088\u003c/li\u003e\n\u003cli\u003eKim H, Hwang Y, Sung H, et al. Effectiveness of Gastric Cancer Screening on Gastric Cancer Incidence and Mortality in a Community-Based Prospective Cohort. \u003cem\u003eCancer Res Treat\u003c/em\u003e. 2018;50(2):582-589. doi:10.4143/crt.2017.048\u003c/li\u003e\n\u003cli\u003eJun JK, Choi KS, Lee HY, et al. Effectiveness of the Korean National Cancer Screening Program in Reducing Gastric Cancer Mortality. \u003cem\u003eGastroenterology\u003c/em\u003e. 2017;152(6):1319-1328.e7. doi:10.1053/j.gastro.2017.01.029\u003c/li\u003e\n\u003cli\u003eGBD 2019 Demographics Collaborators. Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019. \u003cem\u003eLancet\u003c/em\u003e. 2020;396(10258):1160-1203. doi:10.1016/S0140-6736(20)30977-6\u003c/li\u003e\n\u003c/ol\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":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Health inequality, Disability-adjusted life-years (DALYs), Gastrointestinal cancers, Socio-Demographic Index (SDI)","lastPublishedDoi":"10.21203/rs.3.rs-4826804/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4826804/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo explore cross-country inequalities in global disease burdens of colon and rectum cancer (CRC), esophageal cancer (EC) and gastric cancer (GC).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eData from the Global Burden of Diseases Study 2019 were analyzed to examine trends in disability-adjusted life-years (DALYs) for three cancers using Estimated Annual Percentage Change (EAPC) and Joinpoint analysis. Inequality in DALYs rates was assessed with the Slope Index of Inequality and the Concentration Index, based on the Socio-Demographic Index (SDI).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFrom 1990 to 2019, age standardized DALYs rate of CRC decreased in high and high-middle SDI regions, with the EAPC values of -1.018 and \u0026minus;\u0026thinsp;0.161, but increased among low, low-middle and middle SDI regions (EAPC\u0026thinsp;=\u0026thinsp;1.035, 0.926 and 0.406, respectively). The DALYs rates of EC and GC decreased in all SDI regions. For CRC, the slope index changed from 358.42 (95% confidence interval: 343.28 to 370.49) to 245.13 (217.47 to 271.24); from \u0026minus;\u0026thinsp;63.88 (-87.48 to -48.28) to -1.36 (-32.44 to 25.87) for EC; from 126.37 (101.97 to 146.47) to 58.04 (20.54 to 96.12) for GC. The concentration index for CRC moved from 29.56 (28.99 to 29.84) to 23.90 (23.19 to 24.26); from \u0026minus;\u0026thinsp;9.47 (-10.30 to -9.24) to -14.64 (-15.35 to -14.24) for EC; from 8.44 (7.85 to 8.72) to -6.42 (-7.65 to -6.12) for GC.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study suggests strong heterogeneity in global DALYs for gastrointestinal cancers across different SDI regions. Higher SDI regions faced a greater burden of CRC, while the burdens of EC and GC were more prevalent in lower SDI regions.\u003c/p\u003e","manuscriptTitle":"Cross-country inequalities in global burden of gastrointestinal cancers: a slope and concentration index methods","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-30 11:17:29","doi":"10.21203/rs.3.rs-4826804/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-01T04:21:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-30T14:16:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180587170332839588641944006782516036976","date":"2024-10-03T06:04:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-02T17:51:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282766683403235921088147294742536721183","date":"2024-08-26T09:05:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-09T13:53:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-07T16:06:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-06T04:12:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2024-07-30T08:03:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b8775c18-fe68-4525-a4b7-52b01ef9316b","owner":[],"postedDate":"August 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-01-02T07:08:42+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-30 11:17:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4826804","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4826804","identity":"rs-4826804","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}