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Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations

By Jian Carrot-Zhang, Giovanny Soca, Nick J. Patterson, Jackie Watson, Aaron Thorner, Anwesha Nag, Giulio Genovese, July Rodriguez Ariza, Maya K. Gelbard, Luis Corrales-Rodriguez, Yoichiro Mitsuishi, Gavin Ha, Joshua D. Campbell, Geoffrey Oxnard, Oscar Arrieta, Andres F Cardona, Alexander Gusev, Matthew Meyerson

Posted 02 Sep 2020
medRxiv DOI: 10.1101/2020.09.01.20183913

Inherited lung cancer risk, particularly in non-smokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden (TMB), and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score predicted EGFR and KRAS mutation frequency more strongly than global ancestry, suggesting that germline genetics (rather than environmental exposure) underlie these disparities.

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