The Genomics of Colorectal Cancer in Populations with African and European Ancestry.pdf (15.46 MB)
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The genomics of colorectal cancer in populations with African and European ancestry

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journal contribution
posted on 09.06.2022, 15:31 by 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 DasSudipto Das, Leonard Augenlicht, Amit Verma, John M Greally, Srilakshmi M Raj, Sanjay Goel, Siraj M Ali

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.

Funding

StAR Funding | Funder: RCSI | Grant ID: SD_StAR

NIH grant 5K12CA13278312

Paul Calabresi K12 Career Development Award

History

Comments

The original article is available at https://aacrjournals.org/

Published Citation

Myer PA. et al. The genomics of colorectal cancer in populations with African and European ancestry. Cancer Discov. 2022;12(5):1282-1293

Publication Date

2 May 2022

PubMed ID

35176763

Department/Unit

  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Cancer
  • Immunity, Infection and Inflammation

Publisher

American Association for Cancer Research (AACR)

Version

  • Published Version (Version of Record)