Abstract IA-07: Genetic ancestry and lung cancer somatic mutations in patients of Latin American descent: Etiology and treatment implications

Abstract

Abstract Inherited lung cancer risk, particularly in nonsmokers, is poorly understood. In particular, the frequency of somatic EGFR and KRAS mutations in lung cancer varies by ethnicity. Somatic EGFR mutation rates are higher in lung cancers from patients with East Asian ancestry and lower in patients with European or African ancestry. Somatic KRAS mutation rates show the opposite pattern. In patients from Latin America, somatic lung cancer EGFR mutation rates vary by country, highest in countries with more Native American ancestry. To ask whether the somatic genome in lung cancer is affected by ethnicity related germline risk, we studied genomes from 1,153 lung cancers from Mexico and Colombia. This study revealed striking associations between ancestry and somatic lung cancer alterations, including tumor mutational burden, and specific driver mutations in EGFR, KRAS, and STK11. A local ancestry score was more strongly correlated with EGFR mutation frequency compared with global ancestry correlation, suggesting that germline genetics (rather than environmental exposure) underlie these disparities. Our study suggests that the variation in EGFR and KRAS mutation frequency in lung cancer is associated with genetic ancestry in patients from Latin America, and suggests further studies to identify germline alleles that underpin this association. If we find a germline locus, this might help in improving lung cancer prevention and screening for populations of Latin American origin and others. Furthermore, multiple studies now highlight the special importance of EGFR mutation screening and EGFR-directed targeted therapy for lung cancer patients in Latin America and with origins in Latin America. Citation Format: Jian Carrot-Zhang, Giovanny Soca-Chafre, Nick Patterson, Aaron Thorner, Anwesha Nag, Jacqueline Watson, Giulio Genovese, July Rodriguez, Maya Gelbard, Luis Corrales-Rodriguez, Yoichiro Mitsuishi, Gavin Ha, Joshua Campbell, Geoffrey Oxnard, Oscar Arrieta, Andres Cardona, Alexander Gusev, Matthew Meyerson. Genetic ancestry and lung cancer somatic mutations in patients of Latin American descent: Etiology and treatment implications [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA-07.