Comprehensive analysis of Native Hawaiians and Other Pacific Islanders with Early Onset Colorectal Cancer

Comprehensive analysis of Native Hawaiians and Other Pacific Islanders with Early Onset Colorectal Cancer | 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 Comprehensive analysis of Native Hawaiians and Other Pacific Islanders with Early Onset Colorectal Cancer Manasawee Tanariyakul, Chalothorn Wannaphut, Toshiaki Takahashi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5994688/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Jul, 2025 Read the published version in Journal of Gastrointestinal Cancer → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose Rates of early-onset colorectal cancers (EOCRC) are increasing in Hawaii across all racial groups. Previous studies have shown that Native Hawaiians have a higher mortality rate compared to other racial groups, however these studies only performed limited adjustments for sociodemographic factors. Our objective is to conduct a comprehensive analysis of outcomes among patients with EOCRC in a racially diverse population accounting for tumor factors and patient sociodemographics. Method Data were abstracted for patients under the age of 50 years diagnosed with colorectal cancer between 2000 and 2022 in Hawaii. Overall survival of Asians, Whites, and Native Hawaiian or Other Pacific Islanders (NHOPI) was calculated using the Kaplan-Meier method. Cox proportional hazards regression models were created to assess predictors of survival adjusting for clinical and pathological factors. Results A total of 379 patients were included in the final analysis. NHOPI patients more often had Medicaid or were uninsured and their cancers had a higher histopathology grade compared to White and Asian groups. In the unadjusted Cox regression model, NHOPI race, insurance status, grade, and stage were prognostic for survival. However, after adjusting for confounders, having Medicaid or being uninsured, grade, and stage remained prognostic factors, but race was not significantly associated with survival. Conclusion This study concludes that while NHOPI patients with EOCRC demonstrated poorer survival compared to other racial groups, this disparity was largely explained by the large percentage of Medicaid and uninsured NHOPI patients. This study emphasizes the importance of addressing disparities in treatment access and utilization to improve outcomes. Figures Figure 1 Figure 2 Introduction Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. While CRC is most common in older adults, the incidence in individuals over 50 years old has been declining globally, likely due to improved cancer screening. Early onset colorectal cancer (EOCRC) is defined as CRC diagnosed in patients under 50 years old. Paradoxically, the incidence of EOCRC has been rising ( 1 ) . Although the reason for this increase is unknown, several plausible hypotheses have been proposed including exposure to risk factors such as Western-style diet, obesity, physical inactivity, and increased antibiotic use ( 2 ) . The incidence of EOCRC is expected to double further by 2030 ( 3 ) . While up to 20% of EOCRC cases are linked to hereditary cancer syndromes, most patients do not have a genetic predisposition ( 3 ) . With the increasing rates of EOCRC, prognostic factors need to be explored. Race, insurance status, and time to treatment have been implicated as prognostic factors among patients with EOCRC. According to a study of the National Cancer Database, EOCRC patients are more often Black or Hispanic. However, this study did not include an analysis of Asian and Pacific Islanders populations ( 4 ) . A cohort study by Nagata et al found that EOCRC disproportionately affects Native Hawaiians, with Native Hawaiian patients being diagnosed 5–10 years earlier than other racial groups, including Asians (Japanese, Chinese, Filipinos) and Whites. Native Hawaiians also experience higher CRC mortality rates compared to other racial groups. However, the study did not adjust for socioeconomic factors like insurance status ( 5 ) , which significantly impacts survival in patients with EOCRC. A study by Salem et al found that patients without private insurance had worse outcomes compared to those with private insurance ( 6 ) . Another potential prognostic factor is time to treatment, though studies on this topic show conflicting results. A study by Iversen et al found that a therapeutic delay of at least 60 days was a negative prognostic factor for long term survival for rectal cancer but not for colon cancer ( 7 ) . Additionally, a study by Castelo et al reviewed the literature on treatment delays of EOCRC and found no clear evidence showing an association between delays in treatment and worse survival outcomes ( 8 , 9 ) . Despite the significant impact of sociodemographic factors on survival of patients with EOCRC, no study has been conducted in a racially diverse population including Asian and Native Hawaiian and Pacific Islanders (NHOPI) patients with a comprehensive analysis of sociodemographic and treatment factors. This study aims to determine the impact of sociodemographic attributes and treatment variables on the survival of Asian and NHOPI patients with EOCRC. Method A retrospective analysis was performed using data from the Queen’s Medical Center (QMC), Honolulu, Hawaii, Oncology Data Registry (ODR). QMC, the largest hospital in Hawaii, serves as a key center for the care of CRC patients in the state ( 10 , 11 ) . According to the American Cancer Society ( 12 ) , Hawaii is estimated to have 700 new CRC cases in 2022. Of these, 220 patients were diagnosed and treated at QMC, according to 2022 Annual Cancer Registry Report of The Queen’s Medical Center ( 13 ) . ODR was established in 1960 as part of the Hawaii Tumor Registry and has contributed data to the Surveillance, Epidemiology, and End Results program since 1973. All patients diagnosed with CRC between January 1, 2000, and December 31, 2022, who were under 50 years old at the time of diagnosis were eligible for inclusion. Institutional Review Board approval was obtained from QMC. Data collection Data on patient demographics (including age, gender, race, and insurance status), clinicopathologic characteristics, initial diagnosis date, and treatment dates (including surgery, chemotherapy, immunotherapy, and radiation therapy) were collected. Race was self-reported by the patient and documented in the ODR. Patients were categorized into three racial groups: White, Asian (Japanese, Korean, Chinese, Filipino, Asian Indian, Pakistani, Thai, Vietnamese, Cambodian, Laotian, and other Asians) and Native Hawaiian or Other Pacific Islanders (NHOPI; Native Hawaiian, Samoan, Tongan, Micronesian, Marshallese, Fijian, Chamorro, and other Pacific Islander). Patients of other races or with unknown race, who only comprised 2.5% of our study population, were excluded. Regarding insurance status, patients were categorized into two insurance groups: 1) Private insurance and 2) Medicaid and Uninsured. Other insurance status (including Medicare, Tricare and down, VA, Military, and unknown insurance status) accounting for 9.6% were not included in the analysis. Furthermore, patients with in situ staging (0.2%), unknown histopathology grade (9.2%), and unknown tumor location (0.8%) were excluded. Statistical Analyses The primary objective of the study was to determine survival outcome by race among patients diagnosed with EOCRC. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic and tumor data, stratified by race. A two-sided p-value < 0.05 was considered statistically significant. Overall survival (OS) was calculated using the Kaplan-Meier method, and univariate comparisons between racial and insurance groups were performed using the log-rank test. Cox proportional hazards regression models for survival were built to obtain hazard ratios (HR) and 95% confidence interval (CI), adjusting for age, gender, race, insurance status, histologic grade, stage of cancer, time from diagnosis to treatment, and location of tumors. Statistical analyses were performed using IBM SPSS Statistics version 29.0.2.0. Result A total of 379 patients were included in the final analysis. Asian comprised 54.6% (n = 207), White comprised 19.8% (n = 75), and NHOPI comprised 25.6% (n = 97). Males comprised 54.9% (n = 208) and females comprised 45.1% (n = 171). Table 1 summarizes the study population’s demographic, insurance status, clinicopathologic characteristics, and treatment details. Baseline characteristics stratified by each racial group are shown in Table 2 . NHOPI patients more often had Medicaid or were uninsured (p < 0.001) and had tumors with a higher histopathologic grade (p = 0.022). Notably, NHOPI patients were diagnosed at a younger age compared to White and Asian groups although this was not statistically significant (p = 0.069). Kaplan-Meier analysis found that the median OS of NHOPI patients (61 months) was significantly lower (p = 0.003) than that of the Asian (215 months) or White populations (median OS not reached). (Fig. 1 ). The median OS of Medicaid and uninsured group (67 months) was significantly lower compared with private insurance group (215 months) (p < 0.001) (Fig. 2 ). Univariate Cox regression analyses for OS showed that NHOPI patients had significantly shorter survival (White as a reference group) with HR = 2.005 (95% CI: 1.231–3.265, p = 0.005). Medicaid insurance was also found to be an adverse prognostic factor (private insurance as a reference group) with HR = 1.865 (95% CI: 1.331–2.612, p < 0.001). Furthermore, univariate analysis revealed that having stage 3 (HR: 3.255, 95% CI: 1.666–6.359, p < 0.001) or 4 (HR = 14.851, 95% CI = 7.499–29.41, p < 0.001) cancer and histopathologic grade 3–4 (HR = 2.785, 95%CI = 1.958–3.963, p one month (≤ one month as a reference group), left-sided tumor, and rectal tumor (right-sided tumor as a reference group) trended towards a higher risk of death, but these findings were not statistically significant (Table 3 ). Multivariate Cox regression analyses for OS were performed. NHOPI race did not significantly impact survival after adjusting for tumor and sociodemographic variables (HR: 1.051, 95% CI: 0.714–1.547, p = 0.8). Medicaid and uninsured status was a statistically significant predictor of inferior survival (HR: 1.843, 95% CI: 1.285–2.643, p < 0.001) as were grade 3 and 4 (HR: 2.278, 95% CI: 1.571–3.303, p < 0.001), stage 3 (HR: 2.873, 95% CI: 1.447–5.706, p = 0.003), stage 4 (HR: 12.778, 95% CI: 6.283–25.987, p < 0.001), and unknown staging (HR: 3.008, 95% CI: 1.189–7.608, p = 0.02) l (Table 3 ). Neither time to treatment nor tumor location were statistically significant predictors of OS. Discussion In our retrospective study of racially diverse patients with EOCRC, we found that NHOPI had significantly shorter survival, however, this disparity resolved after adjustments for sociodemographics and clinicopathologic factors. To our knowledge, this is the first study to comprehensively examine sociodemographic and treatment factors in a large population of NHOPI patients with EOCRC. Studies have demonstrated racial disparities in EOCRC outcomes especially among NHOPI. A study performed by Nagata et al found that Native Hawaiians are diagnosed with CRC at a younger age than patients of other racial groups. Additionally, they noted that Native Hawaiians have higher cancer specific mortality rates ( 5 ) . A study by Chun et al also reported poorer survival outcomes among Native Hawaiians and Japanese patients compared to White patients ( 14 ) . These studies assessed the impact of age, gender, race, and stage; however, they did not adjust for other known prognostic variables such as insurance status, histopathology grading, and time to treatment, which are included in our study. A study by Salem et al demonstrated a significant worsening of survival in the Black population with EOCRC, even after adjusting for clinicopathologic and socioeconomic factors ( 6 ) . This contrasts with our study, which did not identify race as a significant prognostic factor. The findings from Salem et al. could be explained by differences in study population as their study included a large proportion of Black patients and lacked NHOPI, whereas our study had a significant NHOPI population, but no Black patients were included in the analysis. Worse survival rates among Blacks may be due in part to biologic differences, such as higher KRAS mutation rates, more microsatellite-stable tumors, and an increased number of proximal tumors ( 15 – 17 ) . Studies by Hein et al, Yoon et al, and Acoba et al indicate that Asian and NHOPI populations with CRC do not have a significantly higher KRAS mutation rate compared to White, ( 15 , 18 , 19 ) however, data on microsatellite status in Asian and NHOPI populations are limited. Studies on tumor location in Asian groups imply a higher rate of left-sided tumors. Lin et al ( 20 ) found a predominance of left-side tumor in Asian American, while Sung et al ( 21 ) found more rectal cancers in EOCRC cases. Research on tumor location in NHOPI populations remains limited. A recent study by Demb et al evaluated racial survival disparities among EOCRC patients, adjusting for clinicopathologic factors and socioeconomic factors, including insurance status, marital status, and neighborhood urban-rural status. Although higher mortality observed in NHOPI and Black patients decreased after adjustment, NHOPI (Adjusted HR = 1.34, 95%CI = 1.01–1.76) remained significantly associated with worse survival. In contrast to the findings of Demb et al, our analysis did not reveal a significant racial disparity in survival after adjusting for insurance status, which serves as a practical surrogate for socioeconomic status by reflecting access to healthcare and financial resources. This relationship is supported by Unger et al, who found that even within randomized controlled trials, insurance status remains a significant surrogate for socioeconomic status ( 22 ) . Our populations differed, however, as our cohort included a higher proportion of NHOPI patients with Medicaid and no insurance (45.4%) compared to Demb et al’s (20.7%) (23) . This emphasizes the importance of improving healthcare access and utilization across all populations regardless of insurance coverage. Furthermore, our study implies that the survival disparity in NHOPI is less likely to be attributed to non-modifiable biologic factors. Our study population showed a high proportion of advanced cancer staging in EOCRC with 36.7% at stage III and 18.7% at stage IV. Interestingly, these findings are nearly identical to findings from a study by Saraste et al, which reported that 37.6% of EOCRC patients were at stage III and 17.3% were at stage IV ( 24 ) . A study by Chun et al found that Native Hawaiians were diagnosed with distant metastases significantly more often than localized cancer ( 14 ) . Our study population showed a majority of NHOPI patients with stage III or IV EOCRC however only 23% had distant metastatic disease. Given the rising incidence of EOCRC ( 2 ) and the trend toward later-stage diagnosis ( 24 ) , our study emphasizes the importance of raising awareness of the disease and increasing screening in younger populations, especially those under the age of 50 years old. There were 186 patients in our study, 49% of the study population, who were diagnosed with colorectal cancer between 45 and 49 years old and would have been eligible for CRC screening based on current guidelines. The AGA 2023, ACG 2021, and USPSTF 2021 all recommend starting screening at age 45 for individuals with average risk for CRC. ( 25 – 28 ) . Our study also showed frequent rectal involvement (40.9%) in patients with EOCRC, consistent with findings from Chang et al who reported common rectal involvement in patients with CRC aged less than 40 ( 29 ) , and Willauer et al who found high rates of distal colon or rectal involvement in EOCRC ( 30 ) . Chang et al also found a lower incidence of KRAS mutation and absence of BRAF V600E mutation in EOCRC compared to the control group. Willauer et al reported a higher rate of microsatellite instability, increased TP53 mutations, and significantly fewer APC mutations in EOCRC. These genetic differences may contribute to the more frequent rectal involvement, although further studies are needed to explore the mechanisms to confirm these hypotheses. Having Medicaid or being uninsured is a known adverse prognostic factor for cancer patients. Studies by Yoshikawa et al and Miyazaki et al found worsening outcomes in Medicaid and uninsured patients diagnosed with gastric cancer and breast cancer, respectively ( 31 – 33 ) . Our study, which analyzed a racially diverse population, shows a similar trend. This could be explained by insurance-related differences in treatment, lack of access to colon cancer screening, or limited access to oncology physicians ( 34 ) . Salem et al studied the sociodemographic effects in patients with EOCRC and found that patients with Medicare or Medicaid insurance experienced worse survival. In our study, the HR for overall survival was 1.843 (95% CI: 1.285–2.643), which is higher than the HR of 1.28 (95% CI: 1.22–1.34) reported in Salem, et al. This difference may be attributed to differences in socioeconomic status assessment. Salem et al used composite socioeconomic status measures including income and education, which likely lowered the isolated impact of insurance on survival outcomes, while our study focused solely on insurance status as a surrogate for socioeconomic status, which could lead to a greater impact on survival outcomes. Our study also found a worsening of survival in patients whose time from diagnosis to treatment was longer than one month, although this was not statistically significant. There are conflicting results in the studies regarding this issue. A study by Iversen et al ( 7 ) demonstrated a higher mortality rate in patients with total therapeutic delay more than 60 days. However, a study by Castelo et al found no association between time from presentation to treatment and survival outcome when comparing between a group with overall interval of 12 to 18 weeks to a group with longer interval ( 8 , 9 ) . These discrepancies could be explained by the differences in study populations. Iversen et al included CRC patients of all ages, while our study and Castelo et al focused on EOCRC. Also, the definition of treatment delay differs between studies. While many studies focus on the time from diagnosis to treatment, other factors such as delays from first physician contact to treatment or delays from surgery to adjuvant chemotherapy may also contribute to differences in outcomes. This study has some limitations that should be acknowledged. First, our study was retrospective, which introduces the potential for selection bias. To minimize bias, we included all patients diagnosed within the study time period. Second, tumor registry analyses can also be limited by missing or unknown data. Third, our study relied on self-reported race, which may lead to misclassification, especially those who are multi-racial but are analyzed as a single race ( 35 ) . Furthermore, we did not disaggregate data for each individual Asian races (such as Japanese, Filipinos, Chinese, etc.) or NHOPI groups (such as Native Hawaiian, Chuukese, Samoan, etc.) which could obscure disparities within specific racial groups. Fourth, the underrepresentation of certain racial groups, such as Black and American Indian, limits our ability to draw conclusions about EOCRC outcomes in these populations. Finally, while we adjusted for several clinicopathologic variables, such as tumor stage and grade, other unmeasured prognostic factors, such as comorbidities and molecular mutation status of cancers may have influenced the results. Conclusion This research studied the impact of sociodemographic and clinicopathologic factors on the survival outcomes of patients with EOCRC. Although univariate analysis found significant worsening outcome by NHOPI race, this disparity resolved after adjustments for sociodemographic and clinical variables including insurance status. Improving healthcare access and insurance coverage in Medicaid and uninsured populations could help to address these disparate outcomes. Furthermore, this study contributes to the literature highlighting the importance of increasing awareness of EOCRC and encouraging CRC screening starting at age 45. Declarations Author Contribution Dr Tanariyakul, Dr Wannaphut, Dr Takahashi, and Dr Acoba wrote the main manuscript text. Dr Tanariyakul, Dr Wannaphut and Dr Acoba extracted and analyzed the data. All authors reviewed the manuscript. Acknowledgement Thank you to Queen's Medical Center IRB and Hawaii Oncology data registry, which approved and provided the data. Thank you Dr Noppawit Aiumtrakul for helping with the statistical analysis. Data Availability Data is obtained from Hawaii Oncology Data Registry and the raw data is in excel sheet. The final data analysis was done using IBM SPSS Statistics. References Saraiva MR, Rosa I, Claro I. 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Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Published Journal Publication published 28 Jul, 2025 Read the published version in Journal of Gastrointestinal Cancer → Version 1 posted Editorial decision: Revision requested 07 Apr, 2025 Reviews received at journal 07 Apr, 2025 Reviews received at journal 25 Mar, 2025 Reviewers agreed at journal 10 Mar, 2025 Reviewers agreed at journal 18 Feb, 2025 Reviewers invited by journal 16 Feb, 2025 Editor assigned by journal 16 Feb, 2025 Submission checks completed at journal 14 Feb, 2025 First submitted to journal 09 Feb, 2025 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-5994688","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":416555619,"identity":"930856c5-9ada-40a7-a581-b6a2f0465830","order_by":0,"name":"Manasawee Tanariyakul","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYPACCQZ+CRBtACITCChmg2qRnEGiFqDiG3AhAlp05zc/e/Bzj0Xi5tvNzyR+FFgw8LPnGODVYnaMzdyw55lE4rY7x8wke4AOk+x5Q0gLg5kEzwGglhsJZjd4gFoMbhC0hf2b5B+gls0z0r/d/APUYk9YC4+ZNMiWDRI5ZrfBtkgQ1JJTJi1zQMJ4xo2c8t8yBhI8EmeeFeDXcvj4Nsk3B+pk+2ekbzZ886dOjr89eQNeLTDg2ABl8BClHATsiVY5CkbBKBgFIw8AAADpRRjsXgtUAAAAAElFTkSuQmCC","orcid":"","institution":"University of Hawaiʻi at Mānoa","correspondingAuthor":true,"prefix":"","firstName":"Manasawee","middleName":"","lastName":"Tanariyakul","suffix":""},{"id":416555621,"identity":"2c76c32e-49aa-4bfc-9ce8-640a90ded3d6","order_by":1,"name":"Chalothorn Wannaphut","email":"","orcid":"","institution":"University of Hawaiʻi at Mānoa","correspondingAuthor":false,"prefix":"","firstName":"Chalothorn","middleName":"","lastName":"Wannaphut","suffix":""},{"id":416555622,"identity":"2142509f-b136-4f47-b614-66f0707bfe1a","order_by":2,"name":"Toshiaki Takahashi","email":"","orcid":"","institution":"University of Hawaiʻi at Mānoa","correspondingAuthor":false,"prefix":"","firstName":"Toshiaki","middleName":"","lastName":"Takahashi","suffix":""},{"id":416555623,"identity":"e2b1eff2-b241-4b10-abc1-0358fa6d8211","order_by":3,"name":"Ryon Nakasone","email":"","orcid":"","institution":"University of Hawaiʻi at Mānoa","correspondingAuthor":false,"prefix":"","firstName":"Ryon","middleName":"","lastName":"Nakasone","suffix":""},{"id":416555624,"identity":"e5b45e64-596a-41b6-89fd-4a311c357cdb","order_by":4,"name":"Jared Acoba","email":"","orcid":"","institution":"University of Hawaiʻi at Mānoa","correspondingAuthor":false,"prefix":"","firstName":"Jared","middleName":"","lastName":"Acoba","suffix":""}],"badges":[],"createdAt":"2025-02-10 00:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5994688/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5994688/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12029-025-01278-w","type":"published","date":"2025-07-28T16:38:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":76576090,"identity":"f1a431e1-4308-4cdd-b9d9-bfb093d64ae6","added_by":"auto","created_at":"2025-02-18 14:14:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":88113,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier analysis of overall survival stratified by race\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median overall survival for the Asian group is 215 months (95% CI=152-277 months) while the median overall survival for the NHOPI group is 61 months (95% CI= 26-96 months). The median overall survival for the White group was not reached. \u0026nbsp;The log rank p-value is 0.003.\u003c/p\u003e\n\u003cp\u003eNHOPI: Native Hawaiians and Other Pacific Islanders\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5994688/v1/91828d7f4e04d813b513ef7d.png"},{"id":76576095,"identity":"22a970e5-ea7d-488f-9709-29773478aec1","added_by":"auto","created_at":"2025-02-18 14:14:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":77037,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier analysis of overall survival stratified by insurance status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median overall survival for private insurance group is \u0026nbsp;215 months (95% CI=169-260 months), while for the Medicaid and uninsured group is approximately 67 months (95% CI=46-88 months). The log rank p-value is \u0026lt;0.001.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5994688/v1/eb7ee8d1dbb73c70e4a702f3.png"},{"id":88268859,"identity":"0a7a57dd-56f7-4edd-9800-767505b3fa10","added_by":"auto","created_at":"2025-08-04 16:52:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":613433,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5994688/v1/73342184-d68e-4199-a677-2f56f2ba838f.pdf"},{"id":76576083,"identity":"16950dad-6ea5-44de-be86-e2833a780162","added_by":"auto","created_at":"2025-02-18 14:14:20","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":515313,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-5994688/v1/f96a4c94e3fb904cf0d3aba0.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comprehensive analysis of Native Hawaiians and Other Pacific Islanders with Early Onset Colorectal Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer (CRC) is one of the most prevalent malignancies worldwide. While CRC is most common in older adults, the incidence in individuals over 50 years old has been declining globally, likely due to improved cancer screening. Early onset colorectal cancer (EOCRC) is defined as CRC diagnosed in patients under 50 years old. Paradoxically, the incidence of EOCRC has been rising \u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/sup\u003e. Although the reason for this increase is unknown, several plausible hypotheses have been proposed including exposure to risk factors such as Western-style diet, obesity, physical inactivity, and increased antibiotic use\u003csup\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/sup\u003e. The incidence of EOCRC is expected to double further by 2030\u003csup\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/sup\u003e. While up to 20% of EOCRC cases are linked to hereditary cancer syndromes, most patients do not have a genetic predisposition\u003csup\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/sup\u003e. With the increasing rates of EOCRC, prognostic factors need to be explored.\u003c/p\u003e \u003cp\u003eRace, insurance status, and time to treatment have been implicated as prognostic factors among patients with EOCRC. According to a study of the National Cancer Database, EOCRC patients are more often Black or Hispanic. However, this study did not include an analysis of Asian and Pacific Islanders populations\u003csup\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/sup\u003e. A cohort study by Nagata et al found that EOCRC disproportionately affects Native Hawaiians, with Native Hawaiian patients being diagnosed 5\u0026ndash;10 years earlier than other racial groups, including Asians (Japanese, Chinese, Filipinos) and Whites. Native Hawaiians also experience higher CRC mortality rates compared to other racial groups. However, the study did not adjust for socioeconomic factors like insurance status\u003csup\u003e(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/sup\u003e, which significantly impacts survival in patients with EOCRC. A study by Salem et al found that patients without private insurance had worse outcomes compared to those with private insurance\u003csup\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/sup\u003e. Another potential prognostic factor is time to treatment, though studies on this topic show conflicting results. A study by Iversen et al found that a therapeutic delay of at least 60 days was a negative prognostic factor for long term survival for rectal cancer but not for colon cancer\u003csup\u003e(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/sup\u003e. Additionally, a study by Castelo et al reviewed the literature on treatment delays of EOCRC and found no clear evidence showing an association between delays in treatment and worse survival outcomes\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\u003eDespite the significant impact of sociodemographic factors on survival of patients with EOCRC, no study has been conducted in a racially diverse population including Asian and Native Hawaiian and Pacific Islanders (NHOPI) patients with a comprehensive analysis of sociodemographic and treatment factors. This study aims to determine the impact of sociodemographic attributes and treatment variables on the survival of Asian and NHOPI patients with EOCRC.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eA retrospective analysis was performed using data from the Queen\u0026rsquo;s Medical Center (QMC), Honolulu, Hawaii, Oncology Data Registry (ODR). QMC, the largest hospital in Hawaii, serves as a key center for the care of CRC patients in the state\u003csup\u003e(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/sup\u003e. According to the American Cancer Society\u003csup\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/sup\u003e, Hawaii is estimated to have 700 new CRC cases in 2022. Of these, 220 patients were diagnosed and treated at QMC, according to 2022 Annual Cancer Registry Report of The Queen\u0026rsquo;s Medical Center\u003csup\u003e(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/sup\u003e. ODR was established in 1960 as part of the Hawaii Tumor Registry and has contributed data to the Surveillance, Epidemiology, and End Results program since 1973. All patients diagnosed with CRC between January 1, 2000, and December 31, 2022, who were under 50 years old at the time of diagnosis were eligible for inclusion. Institutional Review Board approval was obtained from QMC.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eData on patient demographics (including age, gender, race, and insurance status), clinicopathologic characteristics, initial diagnosis date, and treatment dates (including surgery, chemotherapy, immunotherapy, and radiation therapy) were collected. Race was self-reported by the patient and documented in the ODR.\u003c/p\u003e \u003cp\u003ePatients were categorized into three racial groups: White, Asian (Japanese, Korean, Chinese, Filipino, Asian Indian, Pakistani, Thai, Vietnamese, Cambodian, Laotian, and other Asians) and Native Hawaiian or Other Pacific Islanders (NHOPI; Native Hawaiian, Samoan, Tongan, Micronesian, Marshallese, Fijian, Chamorro, and other Pacific Islander). Patients of other races or with unknown race, who only comprised 2.5% of our study population, were excluded. Regarding insurance status, patients were categorized into two insurance groups: 1) Private insurance and 2) Medicaid and Uninsured. Other insurance status (including Medicare, Tricare and down, VA, Military, and unknown insurance status) accounting for 9.6% were not included in the analysis. Furthermore, patients with in situ staging (0.2%), unknown histopathology grade (9.2%), and unknown tumor location (0.8%) were excluded.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistical Analyses\u003c/h3\u003e\n\u003cp\u003eThe primary objective of the study was to determine survival outcome by race among patients diagnosed with EOCRC. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic and tumor data, stratified by race. A two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Overall survival (OS) was calculated using the Kaplan-Meier method, and univariate comparisons between racial and insurance groups were performed using the log-rank test. Cox proportional hazards regression models for survival were built to obtain hazard ratios (HR) and 95% confidence interval (CI), adjusting for age, gender, race, insurance status, histologic grade, stage of cancer, time from diagnosis to treatment, and location of tumors. Statistical analyses were performed using IBM SPSS Statistics version 29.0.2.0.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003eA total of 379 patients were included in the final analysis. Asian comprised 54.6% (n\u0026thinsp;=\u0026thinsp;207), White comprised 19.8% (n\u0026thinsp;=\u0026thinsp;75), and NHOPI comprised 25.6% (n\u0026thinsp;=\u0026thinsp;97). Males comprised 54.9% (n\u0026thinsp;=\u0026thinsp;208) and females comprised 45.1% (n\u0026thinsp;=\u0026thinsp;171). Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the study population\u0026rsquo;s demographic, insurance status, clinicopathologic characteristics, and treatment details. Baseline characteristics stratified by each racial group are shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. NHOPI patients more often had Medicaid or were uninsured (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and had tumors with a higher histopathologic grade (p\u0026thinsp;=\u0026thinsp;0.022). Notably, NHOPI patients were diagnosed at a younger age compared to White and Asian groups although this was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.069).\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003c/table\u003e\n\u003cp\u003eKaplan-Meier analysis found that the median OS of NHOPI patients (61 months) was significantly lower (p\u0026thinsp;=\u0026thinsp;0.003) than that of the Asian (215 months) or White populations (median OS not reached). (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The median OS of Medicaid and uninsured group (67 months) was significantly lower compared with private insurance group (215 months) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eUnivariate Cox regression analyses for OS showed that NHOPI patients had significantly shorter survival (White as a reference group) with HR\u0026thinsp;=\u0026thinsp;2.005 (95% CI: 1.231\u0026ndash;3.265, p\u0026thinsp;=\u0026thinsp;0.005). Medicaid insurance was also found to be an adverse prognostic factor (private insurance as a reference group) with HR\u0026thinsp;=\u0026thinsp;1.865 (95% CI: 1.331\u0026ndash;2.612, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Furthermore, univariate analysis revealed that having stage 3 (HR: 3.255, 95% CI: 1.666\u0026ndash;6.359, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) or 4 (HR\u0026thinsp;=\u0026thinsp;14.851, 95% CI\u0026thinsp;=\u0026thinsp;7.499\u0026ndash;29.41, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) cancer and histopathologic grade 3\u0026ndash;4 (HR\u0026thinsp;=\u0026thinsp;2.785, 95%CI\u0026thinsp;=\u0026thinsp;1.958\u0026ndash;3.963, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were associated with lower OS. Time to treatment\u0026thinsp;\u0026gt;\u0026thinsp;one month (\u0026le;\u0026thinsp;one month as a reference group), left-sided tumor, and rectal tumor (right-sided tumor as a reference group) trended towards a higher risk of death, but these findings were not statistically significant (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eMultivariate Cox regression analyses for OS were performed. NHOPI race did not significantly impact survival after adjusting for tumor and sociodemographic variables (HR: 1.051, 95% CI: 0.714\u0026ndash;1.547, p\u0026thinsp;=\u0026thinsp;0.8). Medicaid and uninsured status was a statistically significant predictor of inferior survival (HR: 1.843, 95% CI: 1.285\u0026ndash;2.643, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as were grade 3 and 4 (HR: 2.278, 95% CI: 1.571\u0026ndash;3.303, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), stage 3 (HR: 2.873, 95% CI: 1.447\u0026ndash;5.706, p\u0026thinsp;=\u0026thinsp;0.003), stage 4 (HR: 12.778, 95% CI: 6.283\u0026ndash;25.987, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and unknown staging (HR: 3.008, 95% CI: 1.189\u0026ndash;7.608, p\u0026thinsp;=\u0026thinsp;0.02) l (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Neither time to treatment nor tumor location were statistically significant predictors of OS.\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003c/table\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eIn our retrospective study of racially diverse patients with EOCRC, we found that NHOPI had significantly shorter survival, however, this disparity resolved after adjustments for sociodemographics and clinicopathologic factors. To our knowledge, this is the first study to comprehensively examine sociodemographic and treatment factors in a large population of NHOPI patients with EOCRC.\u003c/p\u003e \u003cp\u003eStudies have demonstrated racial disparities in EOCRC outcomes especially among NHOPI. A study performed by Nagata et al found that Native Hawaiians are diagnosed with CRC at a younger age than patients of other racial groups. Additionally, they noted that Native Hawaiians have higher cancer specific mortality rates \u003csup\u003e(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/sup\u003e. A study by Chun et al also reported poorer survival outcomes among Native Hawaiians and Japanese patients compared to White patients\u003csup\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/sup\u003e. These studies assessed the impact of age, gender, race, and stage; however, they did not adjust for other known prognostic variables such as insurance status, histopathology grading, and time to treatment, which are included in our study.\u003c/p\u003e \u003cp\u003eA study by Salem et al demonstrated a significant worsening of survival in the Black population with EOCRC, even after adjusting for clinicopathologic and socioeconomic factors\u003csup\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/sup\u003e. This contrasts with our study, which did not identify race as a significant prognostic factor. The findings from Salem et al. could be explained by differences in study population as their study included a large proportion of Black patients and lacked NHOPI, whereas our study had a significant NHOPI population, but no Black patients were included in the analysis. Worse survival rates among Blacks may be due in part to biologic differences, such as higher KRAS mutation rates, more microsatellite-stable tumors, and an increased number of proximal tumors \u003csup\u003e(\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/sup\u003e. Studies by Hein et al, Yoon et al, and Acoba et al indicate that Asian and NHOPI populations with CRC do not have a significantly higher KRAS mutation rate compared to White, \u003csup\u003e(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/sup\u003e however, data on microsatellite status in Asian and NHOPI populations are limited. Studies on tumor location in Asian groups imply a higher rate of left-sided tumors. Lin et al\u003csup\u003e(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/sup\u003e found a predominance of left-side tumor in Asian American, while Sung et al\u003csup\u003e(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/sup\u003e found more rectal cancers in EOCRC cases. Research on tumor location in NHOPI populations remains limited.\u003c/p\u003e \u003cp\u003eA recent study by Demb et al evaluated racial survival disparities among EOCRC patients, adjusting for clinicopathologic factors and socioeconomic factors, including insurance status, marital status, and neighborhood urban-rural status. Although higher mortality observed in NHOPI and Black patients decreased after adjustment, NHOPI (Adjusted HR\u0026thinsp;=\u0026thinsp;1.34, 95%CI\u0026thinsp;=\u0026thinsp;1.01\u0026ndash;1.76) remained significantly associated with worse survival. In contrast to the findings of Demb et al, our analysis did not reveal a significant racial disparity in survival after adjusting for insurance status, which serves as a practical surrogate for socioeconomic status by reflecting access to healthcare and financial resources. This relationship is supported by Unger et al, who found that even within randomized controlled trials, insurance status remains a significant surrogate for socioeconomic status\u003csup\u003e(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/sup\u003e. Our populations differed, however, as our cohort included a higher proportion of NHOPI patients with Medicaid and no insurance (45.4%) compared to Demb et al\u0026rsquo;s (20.7%)\u003csup\u003e(23)\u003c/sup\u003e. This emphasizes the importance of improving healthcare access and utilization across all populations regardless of insurance coverage. Furthermore, our study implies that the survival disparity in NHOPI is less likely to be attributed to non-modifiable biologic factors.\u003c/p\u003e \u003cp\u003eOur study population showed a high proportion of advanced cancer staging in EOCRC with 36.7% at stage III and 18.7% at stage IV. Interestingly, these findings are nearly identical to findings from a study by Saraste et al, which reported that 37.6% of EOCRC patients were at stage III and 17.3% were at stage IV\u003csup\u003e(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/sup\u003e. A study by Chun et al found that Native Hawaiians were diagnosed with distant metastases significantly more often than localized cancer\u003csup\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/sup\u003e. Our study population showed a majority of NHOPI patients with stage III or IV EOCRC however only 23% had distant metastatic disease. Given the rising incidence of EOCRC\u003csup\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/sup\u003e and the trend toward later-stage diagnosis \u003csup\u003e(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/sup\u003e, our study emphasizes the importance of raising awareness of the disease and increasing screening in younger populations, especially those under the age of 50 years old. There were 186 patients in our study, 49% of the study population, who were diagnosed with colorectal cancer between 45 and 49 years old and would have been eligible for CRC screening based on current guidelines. The AGA 2023, ACG 2021, and USPSTF 2021 all recommend starting screening at age 45 for individuals with average risk for CRC.\u003csup\u003e(\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur study also showed frequent rectal involvement (40.9%) in patients with EOCRC, consistent with findings from Chang et al who reported common rectal involvement in patients with CRC aged less than 40\u003csup\u003e(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/sup\u003e, and Willauer et al who found high rates of distal colon or rectal involvement in EOCRC\u003csup\u003e(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/sup\u003e. Chang et al also found a lower incidence of KRAS mutation and absence of BRAF V600E mutation in EOCRC compared to the control group. Willauer et al reported a higher rate of microsatellite instability, increased TP53 mutations, and significantly fewer APC mutations in EOCRC. These genetic differences may contribute to the more frequent rectal involvement, although further studies are needed to explore the mechanisms to confirm these hypotheses.\u003c/p\u003e \u003cp\u003eHaving Medicaid or being uninsured is a known adverse prognostic factor for cancer patients. Studies by Yoshikawa et al and Miyazaki et al found worsening outcomes in Medicaid and uninsured patients diagnosed with gastric cancer and breast cancer, respectively\u003csup\u003e(\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e)\u003c/sup\u003e. Our study, which analyzed a racially diverse population, shows a similar trend. This could be explained by insurance-related differences in treatment, lack of access to colon cancer screening, or limited access to oncology physicians\u003csup\u003e(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/sup\u003e. Salem et al studied the sociodemographic effects in patients with EOCRC and found that patients with Medicare or Medicaid insurance experienced worse survival. In our study, the HR for overall survival was 1.843 (95% CI: 1.285\u0026ndash;2.643), which is higher than the HR of 1.28 (95% CI: 1.22\u0026ndash;1.34) reported in Salem, et al. This difference may be attributed to differences in socioeconomic status assessment. Salem et al used composite socioeconomic status measures including income and education, which likely lowered the isolated impact of insurance on survival outcomes, while our study focused solely on insurance status as a surrogate for socioeconomic status, which could lead to a greater impact on survival outcomes.\u003c/p\u003e \u003cp\u003eOur study also found a worsening of survival in patients whose time from diagnosis to treatment was longer than one month, although this was not statistically significant. There are conflicting results in the studies regarding this issue. A study by Iversen et al\u003csup\u003e(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/sup\u003e demonstrated a higher mortality rate in patients with total therapeutic delay more than 60 days. However, a study by Castelo et al found no association between time from presentation to treatment and survival outcome when comparing between a group with overall interval of 12 to 18 weeks to a group with longer interval\u003csup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/sup\u003e. These discrepancies could be explained by the differences in study populations. Iversen et al included CRC patients of all ages, while our study and Castelo et al focused on EOCRC. Also, the definition of treatment delay differs between studies. While many studies focus on the time from diagnosis to treatment, other factors such as delays from first physician contact to treatment or delays from surgery to adjuvant chemotherapy may also contribute to differences in outcomes.\u003c/p\u003e \u003cp\u003eThis study has some limitations that should be acknowledged. First, our study was retrospective, which introduces the potential for selection bias. To minimize bias, we included all patients diagnosed within the study time period. Second, tumor registry analyses can also be limited by missing or unknown data. Third, our study relied on self-reported race, which may lead to misclassification, especially those who are multi-racial but are analyzed as a single race\u003csup\u003e(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e)\u003c/sup\u003e. Furthermore, we did not disaggregate data for each individual Asian races (such as Japanese, Filipinos, Chinese, etc.) or NHOPI groups (such as Native Hawaiian, Chuukese, Samoan, etc.) which could obscure disparities within specific racial groups. Fourth, the underrepresentation of certain racial groups, such as Black and American Indian, limits our ability to draw conclusions about EOCRC outcomes in these populations. Finally, while we adjusted for several clinicopathologic variables, such as tumor stage and grade, other unmeasured prognostic factors, such as comorbidities and molecular mutation status of cancers may have influenced the results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis research studied the impact of sociodemographic and clinicopathologic factors on the survival outcomes of patients with EOCRC. Although univariate analysis found significant worsening outcome by NHOPI race, this disparity resolved after adjustments for sociodemographic and clinical variables including insurance status. Improving healthcare access and insurance coverage in Medicaid and uninsured populations could help to address these disparate outcomes. Furthermore, this study contributes to the literature highlighting the importance of increasing awareness of EOCRC and encouraging CRC screening starting at age 45.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eDr Tanariyakul, Dr Wannaphut, Dr Takahashi, and Dr Acoba wrote the main manuscript text. Dr Tanariyakul, Dr Wannaphut and Dr Acoba extracted and analyzed the data. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThank you to Queen's Medical Center IRB and Hawaii Oncology data registry, which approved and provided the data. Thank you Dr Noppawit Aiumtrakul for helping with the statistical analysis.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is obtained from Hawaii Oncology Data Registry and the raw data is in excel sheet. The final data analysis was done using IBM SPSS Statistics.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSaraiva MR, Rosa I, Claro I. Early-onset colorectal cancer: A review of current knowledge. World J Gastroenterol. 2023;29(8):1289-303.\u003c/li\u003e\n\u003cli\u003eAkimoto N, Ugai T, Zhong R, Hamada T, Fujiyoshi K, Giannakis M, et al. Rising incidence of early-onset colorectal cancer - a call to action. Nat Rev Clin Oncol. 2021;18(4):230-43.\u003c/li\u003e\n\u003cli\u003eSpaander MCW, Zauber AG, Syngal S, Blaser MJ, Sung JJ, You YN, et al. Young-onset colorectal cancer. Nat Rev Dis Primers. 2023;9(1):21.\u003c/li\u003e\n\u003cli\u003eSatpathy Y, Nam P, Moldovan M, Murphy JD, Wang L, Derweesh I, et al. Comparison of Capture Rates of the National Cancer Database Across Race and Ethnicity. JAMA Netw Open. 2023;6(12):e2350237.\u003c/li\u003e\n\u003cli\u003eNagata M, Miyagi K, Hernandez BY, Kuwada SK. Multiethnic Trends in Early Onset Colorectal Cancer. Cancers (Basel). 2024;16(2).\u003c/li\u003e\n\u003cli\u003eSalem ME, Puccini A, Trufan SJ, Sha W, Kadakia KC, Hartley ML, et al. Impact of Sociodemographic Disparities and Insurance Status on Survival of Patients with Early-Onset Colorectal Cancer. Oncologist. 2021;26(10):e1730-e41.\u003c/li\u003e\n\u003cli\u003eIversen LH, Antonsen S, Laurberg S, Lautrup MD. Therapeutic delay reduces survival of rectal cancer but not of colonic cancer. Br J Surg. 2009;96(10):1183-9.\u003c/li\u003e\n\u003cli\u003eCastelo M, Sue-Chue-Lam C, Paszat L, Kishibe T, Scheer AS, Hansen BE, et al. Time to diagnosis and treatment in younger adults with colorectal cancer: A systematic review. PLoS One. 2022;17(9):e0273396.\u003c/li\u003e\n\u003cli\u003eCastelo M, Paszat L, Hansen BE, Scheer AS, Faught N, Nguyen L, et al. Analysis of Time to Treatment and Survival Among Adults Younger Than 50 Years of Age With Colorectal Cancer in Canada. JAMA Netw Open. 2023;6(8):e2327109.\u003c/li\u003e\n\u003cli\u003eBest Hospitals for Colon Cancer Surgery near Honolulu, HI [Available from: https://health.usnews.com/best-hospitals/area/honolulu-hi/colon-cancer-surgery.\u003c/li\u003e\n\u003cli\u003eThe Queen\u0026apos;s Medical Center. 2024.\u003c/li\u003e\n\u003cli\u003eESTIMATED NUMBER OF NEW CANCER CASES AND DEATHS BY STATE-- 2022 2022 [Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cases-and-deaths-by-site-and-state.pdf.\u003c/li\u003e\n\u003cli\u003eCenter QsM. Annual Cancer Registry Report 2022 [Available from: https://www.queens.org/wp-content/uploads/Annual-Report-Annual-Cancer-Registry-Report_-3-12-24_-22.pdf.\u003c/li\u003e\n\u003cli\u003eWai ICBYHHJAC. Disaggregating U.S. Asian and Pacific Islanders: Colorectal cancer. Surgical Oncology Insight. 2024;1(3).\u003c/li\u003e\n\u003cli\u003eHein DM, Deng W, Bleile M, Kazmi SA, Rhead B, De La Vega FM, et al. Racial and Ethnic Differences in Genomic Profiling of Early Onset Colorectal Cancer. J Natl Cancer Inst. 2022;114(5):775-8.\u003c/li\u003e\n\u003cli\u003eXicola RM, Gagnon M, Clark JR, Carroll T, Gao W, Fernandez C, et al. Excess of proximal microsatellite-stable colorectal cancer in African Americans from a multiethnic study. Clin Cancer Res. 2014;20(18):4962-70.\u003c/li\u003e\n\u003cli\u003eSchroy PC, 3rd, Coe A, Chen CA, O\u0026apos;Brien MJ, Heeren TC. Prevalence of advanced colorectal neoplasia in white and black patients undergoing screening colonoscopy in a safety-net hospital. Ann Intern Med. 2013;159(1):13-20.\u003c/li\u003e\n\u003cli\u003eYoon HH, Shi Q, Alberts SR, Goldberg RM, Thibodeau SN, Sargent DJ, et al. Racial Differences in BRAF/KRAS Mutation Rates and Survival in Stage III Colon Cancer Patients. J Natl Cancer Inst. 2015;107(10).\u003c/li\u003e\n\u003cli\u003eAcoba J LC, Leong L. Analysis of KRAS and BRAF mutant colorectal cancers in a multiracial population. Journal of Clinical Oncology. 2012;30.\u003c/li\u003e\n\u003cli\u003eLin MY, Liu WY, Aboulian A, Huntley JB, Etzioni DA, Petrie BA. Characteristics of colorectal cancer among Asian Americans. Am Surg. 2010;76(10):1154-7.\u003c/li\u003e\n\u003cli\u003eSung JJY, Chiu HM, Jung KW, Jun JK, Sekiguchi M, Matsuda T, et al. Increasing Trend in Young-Onset Colorectal Cancer in Asia: More Cancers in Men and More Rectal Cancers. Am J Gastroenterol. 2019;114(2):322-9.\u003c/li\u003e\n\u003cli\u003eSnyder RA, Chang GJ. Insurance Status as a Surrogate for Social Determinants of Health in Cancer Clinical Trials. JAMA Netw Open. 2020;3(4):e203890.\u003c/li\u003e\n\u003cli\u003eDemb J, Gomez SL, Canchola AJ, Qian A, Murphy JD, Winn RA, et al. Racial and Ethnic Variation in Survival in Early-Onset Colorectal Cancer. JAMA Netw Open. 2024;7(11):e2446820.\u003c/li\u003e\n\u003cli\u003eSaraste D, Jaras J, Martling A. Population-based analysis of outcomes with early-age colorectal cancer. Br J Surg. 2020;107(3):301-9.\u003c/li\u003e\n\u003cli\u003eIssaka RB, Chan AT, Gupta S. AGA Clinical Practice Update on Risk Stratification for Colorectal Cancer Screening and Post-Polypectomy Surveillance: Expert Review. Gastroenterology. 2023;165(5):1280-91.\u003c/li\u003e\n\u003cli\u003eShaukat A, Kahi CJ, Burke CA, Rabeneck L, Sauer BG, Rex DK. ACG Clinical Guidelines: Colorectal Cancer Screening 2021. Am J Gastroenterol. 2021;116(3):458-79.\u003c/li\u003e\n\u003cli\u003eForce USPST, Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;325(19):1965-77.\u003c/li\u003e\n\u003cli\u003eQaseem A, Harrod CS, Crandall CJ, Wilt TJ, Clinical Guidelines Committee of the American College of P, Balk EM, et al. Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians (Version 2). Ann Intern Med. 2023;176(8):1092-100.\u003c/li\u003e\n\u003cli\u003eChang DT, Pai RK, Rybicki LA, Dimaio MA, Limaye M, Jayachandran P, et al. Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features. Mod Pathol. 2012;25(8):1128-39.\u003c/li\u003e\n\u003cli\u003eWillauer AN, Liu Y, Pereira AAL, Lam M, Morris JS, Raghav KPS, et al. Clinical and molecular characterization of early-onset colorectal cancer. Cancer. 2019;125(12):2002-10.\u003c/li\u003e\n\u003cli\u003eYoshikawa GT, Miyazaki KS, Acoba JD, Fujii T. Racial and survival disparities in inflammatory breast cancer (IBC) and non-IBC: a population-based study focused on Native Hawaiians and other Pacific Islanders. Front Oncol. 2024;14:1390080.\u003c/li\u003e\n\u003cli\u003eFujii KSMJDAT. Abstract PS7-18: The impact of insurance status on survival in patients with inflammatory breast cancer (IBC) and non-IBC among a unique population in Hawaii Cancer Research. 2021;81(4).\u003c/li\u003e\n\u003cli\u003eYoshikawa GT, Simon N, Nakasone RK, Acoba JD. Disaggregating Data on Pacific Islander Gastric Cancer Patients Reveals Survival Disparity. J Gastrointest Cancer. 2022;53(1):144-50.\u003c/li\u003e\n\u003cli\u003eEllis L, Canchola AJ, Spiegel D, Ladabaum U, Haile R, Gomez SL. Trends in Cancer Survival by Health Insurance Status in California From 1997 to 2014. JAMA Oncol. 2018;4(3):317-23.\u003c/li\u003e\n\u003cli\u003eGomez SL, Glaser SL. Misclassification of race/ethnicity in a population-based cancer registry (United States). Cancer Causes Control. 2006;17(6):771-81.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"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":"journal-of-gastrointestinal-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijgc","sideBox":"Learn more about [Journal of Gastrointestinal Cancer](https://www.springer.com/journal/12029)","snPcode":"12029","submissionUrl":"https://submission.nature.com/new-submission/12029/3","title":"Journal of Gastrointestinal Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5994688/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5994688/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eRates of early-onset colorectal cancers (EOCRC) are increasing in Hawaii across all racial groups. Previous studies have shown that Native Hawaiians have a higher mortality rate compared to other racial groups, however these studies only performed limited adjustments for sociodemographic factors. Our objective is to conduct a comprehensive analysis of outcomes among patients with EOCRC in a racially diverse population accounting for tumor factors and patient sociodemographics.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eData were abstracted for patients under the age of 50 years diagnosed with colorectal cancer between 2000 and 2022 in Hawaii. Overall survival of Asians, Whites, and Native Hawaiian or Other Pacific Islanders (NHOPI) was calculated using the Kaplan-Meier method. Cox proportional hazards regression models were created to assess predictors of survival adjusting for clinical and pathological factors.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 379 patients were included in the final analysis. NHOPI patients more often had Medicaid or were uninsured and their cancers had a higher histopathology grade compared to White and Asian groups. In the unadjusted Cox regression model, NHOPI race, insurance status, grade, and stage were prognostic for survival. However, after adjusting for confounders, having Medicaid or being uninsured, grade, and stage remained prognostic factors, but race was not significantly associated with survival.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study concludes that while NHOPI patients with EOCRC demonstrated poorer survival compared to other racial groups, this disparity was largely explained by the large percentage of Medicaid and uninsured NHOPI patients. This study emphasizes the importance of addressing disparities in treatment access and utilization to improve outcomes.\u003c/p\u003e","manuscriptTitle":"Comprehensive analysis of Native Hawaiians and Other Pacific Islanders with Early Onset Colorectal Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-18 14:14:15","doi":"10.21203/rs.3.rs-5994688/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-07T23:52:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-07T18:46:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-26T03:08:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"209060953003091079274084389092820064465","date":"2025-03-10T12:24:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"324234651229399226666655993437205933950","date":"2025-02-18T22:02:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-02-16T19:51:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-02-16T19:50:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-02-14T10:23:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Gastrointestinal Cancer","date":"2025-02-10T00:36:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-gastrointestinal-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijgc","sideBox":"Learn more about [Journal of Gastrointestinal Cancer](https://www.springer.com/journal/12029)","snPcode":"12029","submissionUrl":"https://submission.nature.com/new-submission/12029/3","title":"Journal of Gastrointestinal Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f65dd1d8-b8a6-4d23-b415-686c67222506","owner":[],"postedDate":"February 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-04T16:49:26+00:00","versionOfRecord":{"articleIdentity":"rs-5994688","link":"https://doi.org/10.1007/s12029-025-01278-w","journal":{"identity":"journal-of-gastrointestinal-cancer","isVorOnly":false,"title":"Journal of Gastrointestinal Cancer"},"publishedOn":"2025-07-28 16:38:13","publishedOnDateReadable":"July 28th, 2025"},"versionCreatedAt":"2025-02-18 14:14:15","video":"","vorDoi":"10.1007/s12029-025-01278-w","vorDoiUrl":"https://doi.org/10.1007/s12029-025-01278-w","workflowStages":[]},"version":"v1","identity":"rs-5994688","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5994688","identity":"rs-5994688","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}