Abstract B097: The contribution of the distribution of consensus molecular subtypes to colorectal cancer mortality disparities

Abstract

The consensus molecular subtypes (CMS) of colorectal cancer (CRC) were identified using gene expression profiling to classify CRCs by underlying biological properties. However, the CMS were trained using data from a primarily homogeneous sample of non-Hispanic white individuals. We hypothesize that there may be racial differences in the distribution and classification of the CMS by race. Herein, we investigate whether differences in the distribution of CMS and underlying gene-expression patterns contribute to the higher CRC mortality experienced by Black CRC patients. Data for this investigation arise from 296 adults with incident CRC identified from a consortium involving participants from the Southern Community Cohort Study and Black Women’s Health Study; 73% self-reported Black race and 45% had household income<$15,000. Incident CRC was identified via linkages to state cancer registries and the National Death Index which was also used for mortality outcomes. RNA was extracted from archival formalin-fixed paraffin-embedded CRC tissue. CMS was predicted following RNA-seq analysis and predicted using the CMSclassifier R package. Cox proportional hazard models were used to estimate the associations between CMS and mortality. Minimally adjusted models adjust for age, sex, race, and cohort. Fully adjusted models for overall mortality additionally adjust for income, alcohol, BMI, marital status, stage, grade, screening, radiation, surgery, and family history of CRC, whereas fully adjusted models for CRC-specific mortality additionally adjust for marital status, stage, grade, smoking status, insurance coverage, surgery, radiation, BMI, and screening. Variables were selected via a post-double selection approach. The distribution of CMS varied by race where Black individuals were less likely than White individuals to present with CMS1 subtype, and more likely to present with an unknown subtype; the Black subgroup had: 9.3% CMS1, 32.4% CMS2, 6.9% CMS3, 33.8% CMS4 and 17.6% with an unclassified subtype, whereas White subgroup had: 20.0% CMS1, 28.8% CMS2, 16.3% CMS3, 28.8% CMS4, and 6.3% unknown subtype. Compared to the CMS1 subtype, CMS4 (HR[95%CI]: 2.11[1.09-4.07]) and unclassified subtype (2.28[1.06-4.92]) are associated with increased risk of mortality. CMS2 and CMS3 were not associated with mortality in any of the models under investigation. There were no statistically significant interactions of race and CMS subtype with mortality outcomes (all p-interaction>0.05). These data suggests that CRC tumors unclassified by the CMS subtyping classification may be associated with an increased risk for mortality, and that unclassified CMS are more common among Black than White Americans, possibly due to distinct tumor mutational profiles in individuals with African Ancestry. We hypothesize that differences in the distribution of tumor characteristics may contribute to CRC outcome disparities. Rida A. Khatri, Michael A. Newton, Oluwatoyosi Ogunmuyiwa, Thomas Lawler, Colin Dewey, Dustin Deming, Jennifer M. Weiss, Richard B. Halberg, Julie R. Palmer, Martha J. Shrubsole, Jessica L. Petrick, Shaneda Warren Andersen. The contribution of the distribution of consensus molecular subtypes to colorectal cancer mortality disparities [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr B097.