Data from Racial/Ethnic and Sex Differences in Somatic Cancer Gene Mutations among Patients with Early-Onset Colorectal Cancer

Abstract

<div>Abstract<p>Molecular features underlying colorectal cancer 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) patients with colorectal cancer (2,016 early-onset colorectal cancer patients: sequencing age <50 years). NHB patients with early-onset nonhypermutated colorectal cancer, but not API patients, had higher adjusted tumor mutation rates than NHW patients. There were significant differences for <i>LRP1B, FLT4, FBXW7, RNF43, ATRX, APC</i>, and <i>PIK3CA</i> mutation frequencies in early-onset nonhypermutated colorectal cancers between racial/ethnic groups. Heterogeneities by race/ethnicity were observed for the effect of <i>APC, FLT4</i>, and <i>FAT1</i> between early-onset and late-onset nonhypermutated colorectal cancer. By sex, heterogeneity was observed for the effect of <i>EP300, BRAF, WRN, KRAS, AXIN2</i>, and <i>SMAD2</i>. Males and females with nonhypermutated colorectal cancer had different trends in <i>EP300</i> mutations by age group. These findings define genomic patterns of early-onset nonhypermutated colorectal cancer by race/ethnicity and sex, which yields novel biological clues into early-onset colorectal cancer disparities.</p>Significance:<p>NHBs, but not APIs, with early-onset nonhypermutated colorectal cancer had higher adjusted tumor mutation rates versus NHWs. Differences for <i>FLT4</i>, <i>FBXW7</i>, <i>RNF43</i>, <i>LRP1B</i>, <i>APC</i>, <i>PIK3CA</i>, and <i>ATRX</i> mutation rates between racial/ethnic groups and <i>EP300</i>, <i>KRAS</i>, <i>AXIN2</i>, <i>WRN</i>, <i>BRAF</i>, and <i>LRP1B</i> mutation rates by sex were observed in tumors of young patients.</p><p><i><a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-22-1464" target="_blank">See related commentary by Shen et al., p. 530</a></i>.</p><p><a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-13-3-ITI" target="_blank">This article is highlighted in the In This Issue feature, p. 517</a></p></div>