Mutational disparities in colorectal cancers of White Americans, Alabama African Americans, And Oklahoma American Indians

Abstract

The high incidence and mortality rates of colorectal cancer (CRC) in Alabama African Americans (AAs) and Oklahoma American Indians (AIs) are recognized as cancer disparities, yet the underlying causes have been poorly demonstrated. By evaluating CRC whole-exome sequencing and mutational profiles, here we report sets of mutated genes whose frequencies differed significantly (p < 0.05) in a race-specific manner. Secondary screening with cancer database identified “survival-critical genes (SCGs)” (i.e., genes whose mutations/alterations are associated with significant differences in the patients’ survival rates) among the differentially mutated genes. Notable SCGs with race-pronounced variants were different from DEGs and their involved pathways included nucleotide catabolism and cell cycle checkpoints for AAs, and extracellular matrix organization for AIs. The inclusion of these SCGs with race-pronounced variants in the clinical CRC next-generation sequencing panels and the development of targeting drugs will serve as refinements for precision medicine to overcome racial disparities in health outcomes of CRC.