Abstract A084: Social determinants of health and colorectal cancer molecular phenotypes: A scoping review

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Abstract Colorectal cancer (CRC) exhibits distinct molecular subtypes driven by underlying genomic alterations, which influence both targeted treatment and clinical outcomes. Emerging evidence suggests that these molecular phenotypes may also be shaped by social determinants of health (SDOH). We synthesized the current literature on the association between SDOH—such as socioeconomic status, healthcare access, and other contextual variables—and molecular phenotypes of CRC. We identified relevant literature from PubMed, Embase, and Scopus databases that addressed SDOH in the context of CRC molecular phenotypes. SDOH were identified using criteria aligned with the U.S. Centers for Disease Control and Prevention’s Healthy People 2030 framework. Studies were included if they analyzed clinically relevant molecular features of CRC, such as microsatellite instability (MSI), somatic mutations, mutation signatures, CpG island methylator phenotype (CIMP), and tumor immune activity. Our initial search identified 3,768 potential publications for inclusion. Publications on these topics increased by year from 2005-2024 as indicated by chi-square test results (P value <0.0001). From a prioritized list of 104 publications, findings show that direct SDOH variables, such as insurance status, were frequently studied in relation with access to biomarker testing for molecular phenotypes. Studies of SDOH variables and molecular phenotypes were limited. More commonly, studies included variables closely tied to SDOH, such as race, ethnicity, and lifestyle factors. Molecular phenotypes studied most often included KRAS somatic mutations and MSI, and, to a lesser extent, CIMP and somatic mutations in BRAF or PIK3CA. We identify a critical need for CRC research that explicitly integrates both SDOH and molecular tumor characteristics. Studies include a narrow range of variables to identify associations between exposures and molecular phenotypes, but SDOH are a broad and complex range of interconnected variables. A framework is needed to describe how SDOH contribute to CRC molecular phenotypes. The disparities in biomarker testing by SDOH indicate that CRC molecular phenotype data do not fully represent the population and this is an additional barrier to interpretation. Understanding how social and structural factors influence molecular phenotypes may enhance our ability to assess cancer risk across all populations, inform preventive strategies, and guide future etiological and mechanistic studies. Citation Format: Nijole P. Tjader, John FP. Bridges, Enrique Velazquez Villarreal. Social determinants of health and colorectal cancer molecular phenotypes: A scoping review [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A084.

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