The Genomics of Colorectal Cancer in Populations with African and European Ancestry

Parvathi A. Myer, Jessica K. Lee, Russell W. Madison, Kith Pradhan, Justin Y. Newberg, Carmen R. Isasi, Samuel J. Klempner, Garrett M. Frampton, Jeffery S. Ross, Jeffrey M. Venstrom, Alexa B. Schrock, Sudipto Das, Leonard H. Augenlicht, Amit K. Verma, John M. Greally, Srilakshmi M. Raj, Sanjay Goel, Siraj M. Ali

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1282-1293
Number of pages12
JournalCancer discovery
Volume12
Issue number5
DOIs
StatePublished - May 2 2022

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'The Genomics of Colorectal Cancer in Populations with African and European Ancestry'. Together they form a unique fingerprint.

Cite this