Journal
Cancer Cell, 2020
Authors
Jian Carrot-Zhang, Nyasha Chambwe, Jeffrey S Damrauer, Theo A Knijnenburg, A Gordon Robertson, Christina Yau, Wanding Zhou, Ashton C Berger, Kuan-Lin Huang, Justin Y Newberg, R Jay Mashl, Alessandro Romanel, Rosalyn W Sayaman, Francesca Demichelis, Ina Felau, Garrett M Frampton, Seunghun Han, Katherine A Hoadley, Anab Kemal, Peter W Laird, Alexander J Lazar, Xiuning Le, Ninad Oak, Hui Shen, Christopher K Wong, Jean C Zenklusen, Elad Ziv, Andrew D Cherniack, Rameen Beroukhim

We evaluated ancestry effects on mutation rates, DNA methylation, and mRNA and miRNA expression among 10,678 patients across 33 cancer types from The Cancer Genome Atlas. We demonstrated that cancer subtypes and ancestry-related technical artifacts are important confounders that have been insufficiently accounted for. Once accounted for, ancestry-associated differences spanned all molecular features and hundreds of genes. Biologically significant differences were usually tissue specific but not specific to cancer. However, admixture and pathway analyses suggested some of these differences are causally related to cancer. Specific findings included increased FBXW7 mutations in patients of African origin, decreased VHL and PBRM1 mutations in renal cancer patients of African origin, and decreased immune activity in bladder cancer patients of East Asian origin.

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