Racial/ethnic and sex differences in somatic cancer gene mutations among patients with early-onset colorectal cancer.

Molecular features underlying colorectal cancer (CRC) disparities remain uncharacterized. Here, we investigated somatic mutation patterns by race/ethnicity and sex among 5,856 non-Hispanic White (NHW), 535 non-Hispanic Black (NHB) and 512 Asian/Pacific Islander (API) CRC patients[2,016 early-onset:sequencing age<50]. NHB patients with early-onset non-hypermutated CRC, but not API patients, had higher adjusted tumor mutation rates than NHW patients. There were significant differences for LRP1B, FLT4, FBXW7, RNF43, ATRX, APC and PIK3CA mutation frequencies in early-onset non-hypermutated CRCs between racial/ethnic groups. Heterogeneities by race/ethnicity were observed for the effect of APC, FLT4 and FAT1 between early-onset and late-onset non-hypermutated CRC. By sex, heterogeneity was observed for the effect of EP300, BRAF, WRN, KRAS, AXIN2 and SMAD2. Males and females with non-hypermutated CRC had different trends in EP300 mutations by age group. These findings define genomic patterns of early-onset non-hypermutated CRC by race/ethnicity and sex, which yields novel biological clues into early-onset CRC disparities.