Colorectal Cancer Disparities Research Articles

Addressing Colorectal Cancer Disparities in Unhoused Populations: A Call for Equitable Access and Compassionate Care

AbstractHousing is essential for health. Unhoused individuals have markedly worse health status than the general population culminating in higher rates of premature mortality. Cancer is a leading cause of death in older unhoused adults. Caring for unhoused patients at risk for or with colorectal cancer poses challenges at every stage of oncologic care: prevention, screening, diagnosis, treatment, and follow-up. These challenges result in later stages at diagnosis and worse overall survival. Health systems can work to advance health equity in colorectal cancer in unhoused patients by improving access to care, transitions of care, health care quality, and focusing on socioeconomic/environmental impact.

Difficulties and Disparities in Colorectal Cancer End-of-Life Care: A Patient's Story

AbstractPatients with advanced colorectal cancer nearing the end of life require a multidisciplinary approach to address the unique challenges they face. Using a case vignette, we outline the various stages of a patient's journey with advanced rectal cancer and the common obstacles to their care as they interface with the medical system. We highlight how Black persons might be vulnerable to differences in screening, treatment, procedural interventions, end-of-life care, and health care decision-making. The article also addresses how health inequities and barriers relating to concordant treatment goals can impact the relationship between patient and surgeon. This vignette illustrates the importance of ensuring a team approach to treatment and the value of early involvement of palliative medicine for patients with advanced colorectal cancer.

Colorectal Cancer Screening Rates at Federally Qualified Health Centers From 2014 to 2022: Incomplete Recovery From COVID-19 and Worsening Disparities.

Federally Qualified Health Centers (FQHC) provide preventive health services such as colorectal cancer (CRC) screening to low-income and underinsured individuals. Overall CRC screening participation in the United States declined during the COVID-19 pandemic and recovered by 2021; however, trends in underresourced settings are unknown. Using Uniform Data System data from 2014 to 2022, we assessed trends in FQHC CRC screening rates nationally, in California, and in Los Angeles County and determined clinic-level factors associated with recent screening rate changes. For each FQHC, we calculated the screening rate change from 2019 to 2020, 2020 to 2021, and 2020 to 2022. We used mixed-effects linear regression to determine clinic-level characteristics associated with each screening rate change. Across all FQHC (n = 1,281), 7,016,181 patients were eligible for CRC screening in 2022. Across the United States and in California, median screening rates increased from 2014 to 2019, severely declined in 2020, and failed to return to prepandemic levels by 2022. Both nationally and in California, CRC screening declined most dramatically from 2019 to 2020 in FQHC serving majority Hispanic/Latino patients or a high proportion of patients experiencing homelessness. From 2020 to 2022, screening rates did not recover completely in US FQHC, with disproportionate recovery among FQHC serving majority non-Hispanic Black patients. CRC screening rates at FQHC did not return to prepandemic levels by 2022, and recovery varied by FQHC patient characteristics. Tailored interventions addressing low and decreasing CRC screening rates in FQHC are urgently needed to mitigate worsening CRC disparities.

Abstract 6682: Bile acid profiles and racial disparities in colorectal cancer: Exploring the protective role of secondary bile acid derivatives

Abstract Background: Colorectal cancer (CRC) is the third leading cause of cancer death in the United States, with diet and gut microbiota-derived bile acids implicated as long-term risk factors. The interplay between bile acids and immune cell differentiation, particularly of macrophages and T-cells, is a crucial aspect of the CRC microenvironment. Given the high-animal-fat diets' influence on the microbiome’s production of hydrophobic secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA), this study investigates the potential immunomodulatory effects of their lower concentrations and their isomers in possibly fostering M2-like macrophage expansion. Methods: Clinical samples were obtained during colonoscopies with no tumor findings at Rush University Medical Center, Chicago. RNA was extracted from colonoscopy biopsies for NanoString RNA expression analysis, while bile acids were isolated from both lyophilized stool and frozen serum samples. To explore the immunological effects of secondary bile acids, the macrophage RAW 264.7 cell line, alongside peritoneal macrophages and bone marrow-derived macrophages (BMDMs) from C57BL/6J mice, were treated with LCA and LCA isomers. Following the bile acid treatment, LPS (100 ng/mL) or IL-4 (40 ng/ml) was added to elicit pro-inflammatory or anti-inflammatory states, respectively. After 48 hours, conditioned media were collected for enzyme-linked immunosorbent assay (ELISA), while cells were analyzed by flow cytometry and rt-qPCR. Results: Contrary to initial hypotheses, the levels of DCA and LCA levels were not significantly different between African American and non-Hispanic White subjects. Notably, allo-isomers and oxo-derivatives of these bile acids, which may promote Treg and M2-like macrophage expansion, were substantially lower in African American subjects. Ex vivo treatments with isoalloLCA and IsoLCA led to notable changes in the M2 macrophage differentiation and shifts in PGE2 production upon exposure to inflammatory or anti-inflammatory stimuli, suggesting a nuanced alteration in the macrophage-mediated inflammatory response. Conclusion: This study highlights a significant ethnic variation in bile acid profiles, with a potential impact on immune modulation and CRC risk. The reduced presence of certain bile acid isomers in African American subjects may influence the risk of CRC through altered macrophage differentiation and function. These findings emphasize the need for personalized dietary and therapeutic strategies to modulate the bile acid metabolome, potentially reducing CRC disparities. Citation Format: Hanchu Dai, Patricia G. Wolf, Lisa Tussing-Humphreys, Ece Mutlu, Jason M. Ridlon, Rex Gaskins. Bile acid profiles and racial disparities in colorectal cancer: Exploring the protective role of secondary bile acid derivatives [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6682.

Abstract 6135: Racial and ethnic differences in site of de novo metastases in patients with colorectal cancer: A SEER analysis

Abstract Purpose: Disparities in colorectal cancer (CRC) mortality may be driven by differences in access to care, tumor biology, and propensity to spread to distant sites. We examine differences in patterns of de novo metastases by race/ethnicity and age. Methods: We identified 248,732 CRC patients listed in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with a first primary invasive CRC from 2010-2020, aged 20+ years at diagnosis, with complete data on SEER summary stage, and not diagnosed only by autopsy/death certificate. Outcomes included de novo metastatic site (no metastasis, liver, lung, brain, bone) and pattern (no metastasis, liver only, lung only, liver and lung, other). We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between 1) demographic and tumor characteristics (site, side, T stage, N stage) and site of de novo metastases , and 2) race/ethnicity and site of de novo metastases stratified by age (20-49, 50-74, 75+). We used multinomial logistic regression to assess the association between demographic and tumor characteristics and pattern of metastasis. Models adjusted for age, race/ethnicity, sex, site (colon, rectum), side (left, right), T stage, and N stage. Results: 62,844 stage IV CRC cases were diagnosed from 2010-2020, and liver was the most common metastatic site (72%). Relative to age 50-74, age 20-49 at diagnosis was more strongly associated with de novo liver metastases (OR: 1.07; 95% CI: 1.02-1.11) and less with lung (OR: 0.86; 95% CI: 0.80-0.92) or brain (OR: 0.69; 95% CI: 0.52-0.93) metastases. Relative to Non-Hispanic White (NHW) patients, Non-Hispanic American Indian/Alaskan Native (AI/AN) patients had a higher risk of lung metastases (OR: 1.33; 95% CI: 1.07-1.65), Non-Hispanic Asian/Pacific Islander (API) patients had lower risks of liver (OR: 0.87; 95% CI: 0.83-0.92) and brain (OR: 0.67; 95% CI: 0.48-0.95) metastases, and Non-Hispanic Black (NHB) patients had higher risks of liver (OR: 1.35; 95% CI: 1.29-1.41), lung (OR: 1.36; 95% CI: 1.27-1.45), and bone (OR: 1.23; 95% CI: 1.08-1.41) metastases. In age-stratified analyses, the risks for NHB patients persisted across groups, while lower risks for API patients were not observed in the 20-49 group. API patients aged 20-49 had a higher risk of de novo lung (OR: 1.31; 95% CI: 1.06-1.61) and bone (OR: 1.63; 95% CI: 1.13-2.37) metastases, and the increased risk of lung metastases for AI/AN patients was larger in magnitude (OR: 2.26; 95% CI: 1.39-3.68). Age 20-49 was more strongly associated with a liver-only pattern (OR: 1.14; 95% CI: 1.09-1.19) and with less common distant sites (OR: 1.33; 95% CI: 1.25-1.41). Conclusions: Racial/ethnic differences in de novo metastatic CRC patterns exist overall and across age groups. These findings are consistent with disparities in risk of stage IV CRC and can inform surveillance priorities in CRC survivors. Citation Format: Nicole C. Loroña, Mariana C. Stern, Stephanie L. Schmit, Jane C. Figueiredo. Racial and ethnic differences in site of de novo metastases in patients with colorectal cancer: A SEER analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6135.

Abstract 6134: The Latino Colorectal Cancer Consortium: A resource for colorectal cancer disparities research

Abstract Purpose: The Latino Colorectal Cancer Consortium (LC3) was established to fill a gap in representation of the diverse Hispanic/Latino/a/x community in cancer genomic research and to enhance understanding of determinants of disparities in the burden of colorectal cancer (CRC). Methods: The LC3 joins together three established studies with deeply-annotated clinical, epidemiologic, and biologic data available for a heterogenous group of Hispanic/Latino/a/x men and women diagnosed with primary colorectal adenocarcinoma: the Hispanic Colorectal Cancer Study (California), the Total Cancer Care Protocol at Moffitt Cancer Center (Florida), and the Puerto Rico Biobank (southern Puerto Rico). Each contributing study collected data on demographics, medical history, family history, and lifestyle factors. Vital status, cause of death, treatment, and clinical characteristics were obtained through medical chart abstraction and/or linkage to cancer registries. Blood, saliva, or normal colonic tissues were used to extract and genotype germline DNA for a subset of participants. Tumor tissues (snap frozen or formalin-fixed paraffin-embedded) were evaluated by pathologists for diagnosis, tissue content, tumor cellularity, necrosis, immune infiltration, and additional histopathologic characteristics. Results: The LC3 has assembled 2,041 participants across the three studies to date, with recruitment ongoing. Median age at diagnosis is 57 (range: 19-93), 54% of participants are male, and 63% are colon cancer cases (vs. rectal cancer). Participants were diagnosed between 1999 and 2022. The target is to generate comprehensive multi-omic data on 600 LC3 participants. To date, 243 have genome-wide germline genotyping, 323 have paired tumor/normal whole exome sequencing, and 257 have T cell receptor immunosequencing (immunoSEQ, Adaptive Biotechnologies). Further, 206 cases are represented on a set of tissue microarray blocks (target N=281). Bulk RNA-seq data are to be generated on 250 tumors. Conclusions: The LC3 fills an important gap in research infrastructure for the scientific community. Key strengths of this unique consortium are its ability to capture a diversity of Latino CRC patients with respect to nativity and cultural heritage and to represent the spectrum of stages from early to metastatic. Ultimately, research from the LC3 will inform development of equitable precision medicine approaches and predictive models to improve the health of the rapidly-growing, heterogeneous Hispanic/Latino/a population. Citation Format: Nicole C. Loroña, Marco Matejcic, Daniel Sobieski, Nathalie T. Nguyen, Hannah J. Hoehn, Diana B. Diaz, Kritika Shankar, Esther Jean-Baptiste, Domenico Coppola, Clifton Fulmer, Ozlen Saglam, Kun Jiang, Teresita Muñoz-Antonia, Idhaliz Flores, Edna Gordian, José A. Oliveras Torres, Seth I. Felder, Julian A. Sanchez, Jason Fleming, Erin M. Siegel, Douglas Cress, Mariana C. Stern, Jamie K. Teer, Stephanie L. Schmit, Jane C. Figueiredo. The Latino Colorectal Cancer Consortium: A resource for colorectal cancer disparities research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6134.

Abstract 1298: Assessing the impact of Medicaid expansion on colorectal cancer preventative services utilization

Abstract Introduction: Colorectal cancer (CRC) is the second leading cause of cancer mortality. CRC screening rates have steadily risen and incidence rates around the nation have declined. To date, forty-one states have expanded Medicaid across the United States, with 9 states remaining that have not expanded. Although, access through insurance has increased, colorectal disparities in screening and mortality persist. Other studies have shown that screening guideline concordance can be inconsistent based on insurance type. Data suggests Medicaid enrollees are more likely to present advanced-stage cancers than those privately enrolled. The screening differences throughout the United States emphasize how complex colorectal cancer disparities are and how insurance may play a role. Aims: Our study aims to investigate the impact of Medicaid expansion on timely CRC screenings, specifically examining whether these effects differ by African Americans, Hispanics, and White Americans. Methods: Data was utilized from the Behavioral Risk Factor Surveillance System (BRFSS) to analyze timely CRC screening data of adults below 138% of the federal poverty level (FPL) of states with different Medicaid expansion statuses. Most recently available data was used in our analysis spanning the years 2014-2022 in all 50 states. States were stratified by dummy variables for Medicaid expansion and non-expansion status. Timely CRC screenings were determined by eligible respondent responses. Difference-in-difference analyses were used to study the effect of Medicaid expansion on timely CRC screenings in states with different Medicaid expansion statuses. Results: Our sample included 60.52% White Americans, 12.22% African Americans, and 16.41% Hispanics in both Medicaid expanded and non-expanded states. Sex and race had significant associations to Medicaid expansion status and timely CRC screenings, particularly when analyzing race for Hispanics and White Americans. Between 2014 and 2022, timely CRC screening for low-income adults in Medicaid expansion states was at 33.15% compared to 23.17% from non-expansion status states. Notably, adults aged 45-64 demonstrated the highest differences in timely CRC screenings for Medicaid-expanded states (12.26% and 18.98%) compared to non-expanded states (9.27% and 13.96%, respectively). Citation Format: Paulette Omeaku. Assessing the impact of Medicaid expansion on colorectal cancer preventative services utilization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1298.

The projected health and economic impact of increased colorectal cancer screening participation among Canadians by income quintile.

Disparities in colorectal cancer (CRC) screening uptake by socioeconomic status have been observed in Canada. We used the OncoSim-Colorectal model to evaluate the health and economic outcomes associated with increasing the participation rates of CRC screening programs to 60% among Canadians in different income quintiles. Baseline CRC screening participation rates were obtained from the 2017 Canadian Community Health Survey. The survey participants were categorized into income quintiles using their reported household income and 2016 Canadian Census income quintile thresholds. Within each quintile, the participation rate was the proportion of respondents aged 50-74 who reported having had a fecal test in the past two years. Using the OncoSim-Colorectal model, we simulated an increase in CRC screening uptake to 60% across income quintiles to assess the effects on CRC incidence, mortality, and associated economic costs from 2024 to 2073. Increasing CRC screening participation rates to 60% across all income quintiles would prevent 69,100 CRC cases and 36,600 CRC deaths over 50 years. The improvement of clinical outcomes would also translate to increased person-years and health-adjusted person-years. The largest impact was observed in the lowest income group, with 22,200 cases and 11,700 deaths prevented over 50 years. Increased participation could lead to higher screening costs ($121 million CAD more per year) and lower treatments costs ($95 million CAD less per year), averaged over the period 2024-2073. Increased screening participation will improve clinical outcomes across all income groups while alleviating associated treatment costs. The benefits of increased participation will be strongest among the lowest income quintile.

Disparities in Colorectal Cancer Incidence among Asian and Pacific Islander Populations in Guam, Hawai'i, and the United States.

Colorectal cancer (CRC) ranks among the three most common cancers in Guam (GU), Hawai'i (HI), and the mainland United States (US). CRC prevalence in these areas is high among Filipinos, and indigenous CHamorus and Native Hawaiians; however, data on these populations are frequently aggregated in epidemiological studies, which can mask true CRC disparities. We examined CRC cumulative incidence rates (CIRs) among CHamorus in GU, Filipinos in GU, HI, and the US, and Native Hawaiians in HI and the US. CRC CIRs were calculated for two age groups (20-49 years; early onset, and 50-79 years; senior) and four time periods (2000-2004, 2005-2009, 2010-2014, and 2015-2019), stratified by ethnicity, sex, and location. Data analyzed included all invasive CRC cases reported to the Surveillance, Epidemiology, and End Results 9-Registry (n = 166,666), the Hawai'i Tumor Registry (n = 10,760), and the Guam Cancer Registry (n = 698) between 2000 and 2019. Senior CIRs were highest in HI and lowest in GU throughout all time periods, with a downward trend observed for senior CIRs in the US and HI, but not GU. This downward trend held true for all ethnic groups, except for CHamorus in GU, females in GU, and females of CHamoru ethnicity in GU. In contrast, early onset CIRs increased across all locations, sexes, and ethnic groups, except for Filipinos in HI and males of Filipino ethnicity in HI. Our findings provide crucial insights for future research and policy development aimed at reducing the burden of CRC among indigenous populations.

Rural-Urban Disparities in Colorectal Cancer Screening, Diagnosis, Treatment, and Survivorship Care: A Systematic Review and Meta-Analysis.

Rural residents have a higher prevalence of colorectal cancer (CRC) mortality compared to urban individuals. Policies have been aimed at improving access to CRC screening to reduce these outcomes. However, little attention has been paid to other determinants of CRC-related outcomes, such as stage at diagnosis, treatment, or survivorship care. The main objective of this analysis was to evaluate literature describing differences in CRC screening, stage at diagnosis, treatment, and survivorship care between rural and urban individuals. We conducted a systematic review of electronic databases using a combination of MeSH and free-text search terms related to CRC screening, stage at diagnosis, treatment, survivorship care, and rurality. We identified 921 studies, of which 39 were included. We assessed methodological quality using the ROBINS-E tool and summarized findings descriptively. A meta-analysis was performed of studies evaluating CRC screening using a random-effects model. Seventeen studies reported disparities between urban and rural populations in CRC screening, 12 on treatment disparities, and 8 on staging disparities. We found that rural individuals were significantly less likely to report any type of screening at any time period (pooled odds ratio = 0.81, 95% CI, 0.76-0.86). Results were inconclusive for disparities in staging at diagnosis and treatment. One study reported a lower likelihood of use of CRC survivorship care for rural individuals compared to urban individuals. There remains an urgent need to evaluate and address CRC disparities in rural areas. Investigators should focus future work on assessing the quality of staging at diagnosis, treatment, and survivorship care in rural areas.

A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer.

The purpose of this work is to investigate the racial disparities in colorectal cancer between Black/AA and White patient cohorts using a systems biology and bioinformatic approach. Our study investigates the underlying biology of each patient cohort. Concretely, the findings of this study include disparity-associated genes and pathways, which provide a tangible starting point to guide precision medicine approaches tailored specifically for colorectal cancer racial disparities.

Factors associated with prior completion of colorectal cancer and hepatitis C virus screenings among community health center patients: a cross-sectional study to inform a multi-behavioral educational intervention.

Colorectal cancer (CRC) and liver cancer are two of the leading causes of cancer death in the United States and persistent disparities in CRC and liver cancer incidence and outcomes exist. Chronic hepatitis C virus (HCV) infection is one of the main contributors to liver cancer. Effective screening for both CRC and HCV exist and are recommended for individuals based upon age, regardless of gender or sex assigned at birth. Recommendations for both screening behaviors have been recently updated. However, screening rates for both CRC and HCV are suboptimal. Targeting adoption of multiple screening behaviors has the potential to reduce cancer mortality and disparities. To examine psychosocial factors associated with completion of CRC and HCV screenings in order to inform a multi-behavioral educational intervention that pairs CRC and HCV screening information. A cross-sectional survey was conducted with participants (N = 50) recruited at two community health centers in Florida (United States). Kruskal-Wallis and Fisher's exact tests were used to examine associations between completion of both CRC and HCV screening, CRC and HCV knowledge, Preventive Health Model constructs (e.g., salience and coherence, response efficacy, social influence), and sociodemographic variables. Most participants were White (84%), female (56%), insured (80%), and reported a household income of $25,000 or less (53%). 30% reported ever previously completing both CRC and HCV screenings. Prior completion of both screening behaviors was associated with higher educational attainment (p = .014), having health insurance (p = .022), being U.S.-born (p = .043), and higher salience and coherence scores for CRC (p = .040) and HCV (p = .004). Findings demonstrate limited uptake of both CRC and HCV screenings among adults born between 1945 and 1965. Uptake was associated with multiple sociodemographic factors and health beliefs related to salience and coherence. Salience and coherence are modifiable factors associated with completion of both screening tests, suggesting the importance of incorporating these health beliefs in a multi-behavioral cancer education intervention. Additionally, health providers could simultaneously recommend and order CRC and HCV screening to improve uptake among this age cohort.

Abstract C075: Socioeconomic status and genetic ancestry correlate with differences in clinical outcomes for colorectal cancer patients treated at a single tertiary cancer center

Abstract Intro:  Lower socioeconomic status (SES) and African ancestry have been linked to poor overall survival (OS) in colorectal cancer (CRC).  To better understand the interplay between these variables, we analyzed clinical and genomic real-world data from a large cohort of patients treated at a single tertiary center.  Methods: Clinical annotations including sex, primary tumor location, age and stage at diagnosis were extracted from the electronic health record for 3,817 CRC patients who underwent clinical genomic sequencing at Memorial Sloan Kettering Cancer Center between 2014 and 2022. We also cataloged each patient’s type of primary health insurance (commercial, Medicare, Medicaid or self-pay). Socioeconomic status was assessed from each patient’s billing address using the Yost index (YI), which is a location-dependent percentile score based on household incomes, house values, rent, poverty, education, and employment statistics.  Genetic ancestry was determined from DNA sequencing data using reference populations from the 1000 Genomes project, including European (EUR), African (AFR), East Asian (EAS), and Southeast Asian (SAS). Specific ancestries were assigned based on an ancestral fraction of >80%, otherwise patients were labeled as admixed (ADM). OS was measured from time of diagnosis to last follow-up. Results: Our cohort included 2,627 EUR, 195 EAS, 206 AFR, 61 SAS and 728 ADM patients. The median YI within our cohort was 18 [IQR: 30]. No significant associations were observed between YI and primary tumor location, age or stage at diagnosis.  We observed significant differences in YI based on type of health insurance (median 15 for commercial vs. 29 for Medicaid, p<0.0001) and sex (median 15 in males vs. 17 in females, p=0.0113). YI was also strongly associated with genetic ancestry, with AFR patients exhibiting significantly higher YI values than other ancestries (median 45.5 vs. 14, p<0.0001). No significant differences in YI were observed among EUR, EAS and SAS patients.  When all ancestries were analyzed together, patients within the bottom YI quartile (most affluent) had significantly longer OS than patients from the top YI quartile (most deprived) (median 52.3 vs. 61.6 months, p=0.023). No differences in OS were observed between EUR, EAS and SAS patients, but patients of AFR ancestry had significantly shorter OS than the rest (median 44.5 vs. 56.5 months, p= 0.016).  When the analysis was restricted to patients of EUR, EAS and SAS ancestry, OS was still significantly shorter for patients within the top vs. bottom YI quartile (median 52.6 vs. 64.4 months, p=0.011).  Conclusions: Patients of African ancestry exhibited lower socioeconomic status and shorter survival.  Even when the analysis was restricted to other genetic ancestries, patients with the lowest socioeconomic status still had poorer clinical outcomes. The existence of these differences within a relatively homogeneous cohort of patients treated at the same institution highlights the need to better understand and address health disparities in CRC. Citation Format: Tejiri Agbamu, Xuechun Bai, Henry Walch, Michele Waters, Anisha Luthra, Kanika Arora, Christopher Fong, Doori Rose, Hannah Williams, Michael Berger, Karuna Ganesh, Julio Garcia-Aguilar, Nikolaus Schultz, Rona Yaegar, Walid Chatila, Francisco Sanchez-Vega. Socioeconomic status and genetic ancestry correlate with differences in clinical outcomes for colorectal cancer patients treated at a single tertiary cancer center [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C075.

Abstract B074: A biobank of fecal immunochemical tests (FIT) to study gut microbiome-mediated cancer disparities

Abstract Introduction: Colorectal cancer (CRC) poses a disproportionate burden among certain Hispanic/Latino subgroups, such as Puerto Rican and Cuban individuals, and Black individuals. Causes of CRC disparities are poorly understood but are likely driven by social determinants of health (SDOH), which may directly and indirectly influence the gut microbiome (GM). In turn, the GM is increasingly implicated in colorectal carcinogenesis. Therefore, it is plausible that the GM may be targeted to reduce excess CRC burden among disproportionately affected populations. However, prior studies of the GM and CRC had limited inclusion of underserved populations and limited collection of SDOH data. Objective: To clearly define the role of the GM in CRC and other cancer disparities, we conducted a pilot study to establish a well-annotated cohort that includes longitudinally collected fecal specimens among diverse populations. Methods: We leveraged fecal immunochemical tests (FIT), a cost-effective method for CRC screening in patient populations with limited access to colonoscopy, in which the GM can be well characterized. Participants completed annual FIT testing following standard protocols as implemented in a Federally Qualified Health Center. FIT samples were processed and banked at Moffitt Cancer Center in -80ºC freezers. All participants completed stool and risk factor questionnaires capturing SDOH, medical history, diet, and lifestyle exposures. To further validate the FIT microbiome, we extracted DNA from 8 sets of triplicate FIT aliquots (200ul each) using the automated MagCore®️ DNA Kit and then performed shotgun sequencing to characterize the fecal microbiome. To test for quality of the data and to compare microbiome metrics (e.g., alpha diversity and microbial abundances) in replicate samples, we calculated intraclass correlation coefficients (ICCs) using linear mixed effects models. Results: In just one clinic, to date, more than N=79 individuals who are primarily Spanish speakers and persons from other racial/ethnic minority subgroups have been enrolled. The racial and ethnic distribution included 39% Mexican, 11% Black, 6% Puerto Rican, 9% Central or South American, and 5% Cuban individuals. Approximately, 59% of the consented population preferentially spoke Spanish and 14% tested positive on the FIT. In the pilot FIT testing samples, we found that the integrity of the DNA was high, with only a few (N=3 of 24) samples with insufficient DNA yield for shotgun metagenomic sequencing. ICCs were generally above ≥ 95% for alpha diversity metrics and abundance of species/genes indicating excellent handling and processing procedures for FIT microbiome extraction and sequencing. Conclusion: Our findings support the concept that FIT-based community screening programs offer exceptional opportunity for GM research in diverse, underrepresented populations. Our future studies will integrate the SDOH data and expand this cohort with the goal of contributing novel insights regarding associations of the GM with early pathogenesis of CRC across diverse populations.  Citation Format: Doratha Byrd, Stephanie Hogue, Xuefeng Wang, Sugriva Forsyth, Martha Fuentes, Kathleen Egan, Tiffany Carson, Youngchul Kim, Jessica Islam, Cathy Meade, Clement Gwede. A biobank of fecal immunochemical tests (FIT) to study gut microbiome-mediated cancer disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B074.

Abstract C051: Deciphering the role of stress-survival pathway genes and mutations in Hispanic colorectal cancer disparities

Abstract This study aims to determine the role of stress-survival pathway (SSP) genes and the associated mutations in Hispanic colorectal cancer (CRC) disparities, particularly in young and late-stage Hispanic CRC. CRC is the second most-deadliest among all cancers and the third leading cause of cancer in the United States (US).  An overall reduction in CRC cases among individuals aged 50 and older has been reported, albeit there is an alarming rise in the incidence of early-onset (patients under the age of 50) CRC. The increase in the early onset of CRC is concerning as these cases tend to appear with higher pathologic grades and have a higher risk of recurrence and metastasis. The incidence of early-onset CRC is almost two times in Hispanics (16.5%) when compared to that in non-Hispanic White (NHWs; 8.7%). Access to health care for Hispanics is limited, as a result, they also tend to present with later-stage CRC when compared to NHWs (32% versus 19% of Stage IV), which likely accounts for their inferior age-adjusted survival after CRC diagnosis. Since Hispanics have the highest percentage of young people and comprise ~18% of the US population, the rising incidence of early-onset and late-stage detection of CRC among Hispanics coupled with the rapid growth in this segment of the population makes it imperative to correctly assess the causes behind the observed disparities in Hispanics with early-onset and late-stage CRC. Our previous study, using in-silico analyses of CRC datasets, helped us identify twenty-eight oxidative stress-response and apoptosis-associated genes that are expressed differently in CRC when compared to normal colon tissues. Expressions of these SSP genes (mRNA and protein levels) were validated in CRC cell lines, cDNA arrays, and human colon cancer tissue microarrays (TMAs). Finally, we have confirmed the differential expression of all twenty-eight transcripts in Hispanic and NHW CRC, and corresponding normal adjacent to the tumor (NAT) tissues. Interestingly, we have identified distinct transcripts that are differentially expressed in Hispanics with early-onset (PDCD2L, CDK1, and PRDX4) and late-stage (CCNB1, CDK4, CHEK1, and MCM10) CRC. We have also identified the mutations associated with the SSP genes by analyzing the ClinVar and NHGRI-EBI GWAS databases. These findings have laid the foundation to characterize further, the roles played by these genes in the molecular basis for Hispanic CRC disparities at early-onset and late stages. Differential Expression of mRNAs in CRC tissues between the two ethnic groups (Hispanics and NHW) and corresponding NATs has been determined by RNA-seq. Ingenuity Pathway Analysis (IPA) has been performed to correlate SSP genes with the canonical CRC pathways to better understand the roles played by these genes, their effects on the downstream cancer-related pathways, and on the early-onset and late-stage Hispanic CRC. These putative ethnicity-specific biomarkers or targets could be used for developing novel prognostic tools or therapeutic interventions for Hispanic CRC patients in the future. Citation Format: Sourav Roy, Brian I. Grajeda, Md Zahirul Islam Khan, Urbashi Basnet, Soumya Nair. Deciphering the role of stress-survival pathway genes and mutations in Hispanic colorectal cancer disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C051.

Type 2 Diabetes and Colorectal Cancer Risk

ImportanceType 2 diabetes and colorectal cancer (CRC) disproportionately burden indviduals of low socioeconomic status and African American race. Although diabetes is an emerging CRC risk factor, associations between diabetes and CRC in these populations are understudied.ObjectiveTo determine if diabetes is associated with CRC risk in a cohort representing understudied populations.Design, Setting, and ParticipantsThis cohort study uses data from the prospective Southern Community Cohort Study in the US, which recruited from 2002 to 2009 and completed 3 follow-up surveys by 2018. Of about 85 000 participants, 86% enrolled at community health centers, while 14% were enrolled via mail or telephone from the same 12 recruitment states. Participants with less than 2 years of follow-up, previous cancer diagnosis (excluding nonmelanoma skin cancer) at enrollment, missing enrollment diabetes status, diabetes diagnosis before age 30, and without diabetes at enrollment with no follow-up participation were excluded. Data were analyzed from January to September 2023.ExposuresPhysician-diagnosed diabetes and age at diabetes diagnosis were self-reported via survey at enrollment and 3 follow-ups.Main Outcomes and MeasuresDiabetes diagnosis was hypothesized to be positively associated with CRC risk before analysis. Incident CRC was assessed via state cancer registry and National Death Index linkage. Hazard ratios and 95% CIs were obtained via Cox proportional hazard models, using time-varying diabetes exposure.ResultsAmong 54 597 participants, the median (IQR) enrollment age was 51 (46-58) years, 34 786 (64%) were female, 36 170 (66%) were African American, and 28 792 (53%) had income less than $15 000 per year. In total, 289 of 25 992 participants with diabetes developed CRC, vs 197 of 28 605 participants without diabetes. Diabetes was associated with increased CRC risk (hazard ratio [HR], 1.47; 95% CI, 1.21-1.79). Greater associations were observed among participants without colonoscopy screening (HR, 2.07; 95% CI, 1.16-3.67) and with smoking history (HR, 1.62; 95% CI, 1.14-2.31), potentially due to cancer screening differences. Greater associations were also observed for participants with recent diabetes diagnoses (diabetes duration <5 years compared with 5-10 years; HR, 2.55; 95% CI, 1.77-3.67), possibly due to recent screening.Conclusions and RelevanceIn this study where the majority of participants were African American with low socioeconomic status, diabetes was associated with elevated CRC risk, suggesting that diabetes prevention and control may reduce CRC disparities. The association was attenuated for those who completed colonoscopies, highlighting how adverse effects of diabetes-related metabolic dysregulation may be disrupted by preventative screening.

627P Racial disparities in synchronous and metachronous colorectal and prostate cancer: SEER based study 2000-2020

627P Racial disparities in synchronous and metachronous colorectal and prostate cancer: SEER based study 2000-2020

Effect of Medicaid Expansion in Reducing Racial Disparities in Early Onset Colorectal Cancer.

The burden of early onset colorectal cancer (EOCRC) falls disproportionately on minorities and individuals in specific geographic regions. While these disparities are likely multi-factorial, access to high-quality health care plays a significant role. We sought to determine if Medicaid expansion is associated with reducing racial disparities in EOCRC detection in Hispanics and non-Hispanic Blacks (NHB), compared to non-Hispanic Whites (NHW). Analysis of data from National Cancer Database was undertaken to compare incidence of EOCRC among those aged 40-49 between Medicaid expansion states (ES) and non-expansion states (NES) by racial/ethnic groups. Data was classified by race (NHW, NHB, or Hispanic), state of residence (ES or NES), and time (pre- or post-expansion). The primary outcome was change in incidence rate of EOCRC among racial/ethnic groups, according to whether patients resided in Medicaid expansion or non-expansion states. Among Hispanics, the ES showed a significant increase in EOCRC incidence post expansion as compared to NES (p = 0.03). The rate of increase in annual incidence of EOCRC among Hispanics was 4.3% per year (pre-expansion) and 9.8% (post-expansion) for ES; and 6.4% (pre-expansion) and 1% (post-expansion) in NES. However, no difference was noted among NHB (p = 0.33) and NHW (p = 0.94). Medicaid expansion has improved detection rates of EOCRC in ES especially in Hispanic population. This is the first study to demonstrate the effect of Medicaid expansion on the incidence of EOCRC. Based on our study findings we suggest that racial and ethnic disparities should be considered in the earlier CRC screening debates.

Associations between the Gut Microbiota, Race, and Ethnicity of Patients with Colorectal Cancer: A Pilot and Feasibility Study.

Colorectal cancer (CRC) is more prevalent among some racial and ethnic minority and low socioeconomic status populations. Although the gut microbiota is a risk factor for CRC and varies with race and ethnicity, its role in CRC disparities remains poorly understood. We examined the feasibility of recruiting sociodemographically diverse CRC patients for a microbiome study involving a home stool collection. We also explored whether race and ethnicity were associated with gut microbiome composition. We recruited Black/African American, Hispanic/Latino, and non-Hispanic White patients who were receiving care for active CRC to complete a comprehensive dietary and lifestyle survey, self-collect a stool sample, and complete an exit interview. Gut microbial diversity and composition were analyzed using 16S rRNA gene sequencing. 30 individuals consented (of 35 who were eligible and contacted) with 5 (17%) Black/African American, 11 (37%) Hispanic/Latino, and 14 (46%) non-Hispanic White. A total of 22 (73%) completed the dietary and lifestyle survey; 18 (63%) returned a stool sample. Even after controlling for socioeconomic, dietary, or treatment-related covariates, microbiome composition was associated with race and ethnicity. Fusobacteriota (a phylum associated with the development and progression of CRC) was significantly higher in the Black/African American group compared to others, and microbial diversity was higher in samples from non-Hispanic White individuals compared to Hispanic/Latino individuals. Our study shows that it is feasible to recruit and collect stool samples from diverse individuals with CRC and found significant associations in gut microbial structure with race and ethnicity.

Colorectal cancer disparities in Latin America: Mortality trends 1990-2019 and a paradox association with human development.

Colorectal cancer mortality is growing in Latin America. It is known for a marked income disparity between its countries, and there is a consistent association with development. Our purpose was to describe trends in colorectal cancer mortality in Latin America between 1990 and 2019, identifying differences by human development categories. We extracted age-adjusted mortality rate from the Global Burden of Disease (GBD) Study from 22 Latin American countries, subregions, and country groups previously ranked by the GBD study due to Sociodemographic Index (SDI) between 1990 and 2019. We applied the segmented regression model to analyze the time trend. Also, we estimated the correlation between mortality rates and Human Development Index (HDI) categories for countries. Between 1990 and 2019, colorectal cancer adjusted mortality rate increased by 20.56% in Latin America (95% CI 19.75% - 21.25%). Between 1990 and 2004, the average annual percentage change (APC) was 0.11% per year (95% CI 0.10-0.12), and between 2004 and 2019 there was a deceleration (APC = 0.04% per year, 95% CI 0.03%- 0.05%). There is great heterogeneity among the countries of the region. Correlation between these two variables was 0.52 for 1990 and 2019. When separated into HDI groups, the correlation varied in the direction of the association and its magnitude, typifying an effect modification known as Simpson's Paradox. Human development factors may be important for assessing variation in cancer mortality on a global scale. Studies that assess the social and -economic contexts of countries are necessary for robust evaluation and provision of preventive, diagnostic and curative services to reduce cancer mortality in Latin America.