Aggressive colorectal cancer subtypes and social disadvantage in a racially diverse cohort

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ABSTRACT While overall colorectal cancer (CRC) incidence and mortality have declined over the last several decades, CRC incidence and mortality rates continue to be higher in African Americans (AAs) than non-Hispanic Whites (NHW). Consensus CRC molecular tumor subtypes are important indicators of carcinogenic pathway and prognosis, and area associated with specific somatic gene mutations, mismatch repair (MMR) phenotype, and gene-specific methylation, although it is currently unknown whether racial differences in these subtypes underlie racial disparities in CRC survival as these subtypes were derived from studies largely comprised of NHW CRCs. The relative contributions of genetic, behavioral and environmental factors on CRC-related outcomes in AA individuals remain largely unknown and there is a critical need for information about pathogenesis to improve approaches to screening and treatment. This is especially true for area-level socioeconomic factors, such as income and housing values, that are associated with higher risk of CRC but for which the biologic consequences are not yet known. The overall goal of the study is to identify genomic and social factors associated with CRC pathogenesis in a well-characterized cohort of AA CRC cases. We hypothesize that tumor biology, here defined by somatic and epigenetic alterations in tumors, explains a substantial proportion of the racial disparities in CRC outcomes, and area-level factors modify this relationship. Our long-term goal is to improve our ability to diagnose, treat and prevent CRC through a comprehensive understanding of the molecular events in tumors that arise in diverse populations.