The genomics of colorectal cancer in populations with African and European ancestry
Black people have a higher incidence of colorectal cancer and worse survival rates when compared with white people. Comprehensive genomic profiling was performed in 46,140 colorectal adenocarcinoma cases. Ancestry-informative markers identified 5,301 patients of African descent (AFR) and 33,770 patients of European descent (EUR). AFR were younger, had fewer microsatellite instability-high (MSI-H) tumors, and had significantly more frequent alterations in KRAS, APC, and PIK3CA. AFR had increased frequency of KRAS mutations, specifically KRASG12D and KRASG13. There were no differences in rates of actionable kinase driver alterations (HER2, MET, NTRK, ALK, ROS1, and RET). In patients with young-onset colorectal cancer (<50 years), AFR and EUR had a similar frequency of MSI-H and tumor mutational burden-high (TMB-H) tumors, and strikingly different trends in APC mutations by age, as well as differences in MAPK pathway alterations. These findings inform treatment decisions, impact prognosis, and underscore the need for model systems representative of the diverse U.S. population.
Significance: KRAS (particularly KRASG12D/G13), APC, and PIK3CA were more frequently altered in AFR who had a lower frequency of MSI-H tumors. There were no differences in actionable kinase driver alterations. In young-onset colorectal cancer, both ancestries had a similar frequency of MSI-H/TMB-H tumors, but strikingly different trends in APC. See related commentary by Eng and Holowatyj, p. 1187. This article is highlighted in the In This Issue feature, p. 1171.
StAR Funding | Funder: RCSI | Grant ID: SD_StAR
NIH grant 5K12CA13278312
Paul Calabresi K12 Career Development Award
CommentsThe original article is available at https://aacrjournals.org/
Published CitationMyer PA. et al. The genomics of colorectal cancer in populations with African and European ancestry. Cancer Discov. 2022;12(5):1282-1293
Publication Date2 May 2022
- School of Pharmacy and Biomolecular Sciences
- Immunity, Infection and Inflammation
PublisherAmerican Association for Cancer Research (AACR)
- Published Version (Version of Record)