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AACR 2022: Can Somatic Mutations and Ancestry Provide Risk Clues in Latin American Patients?

By: Celeste L. Dixon
Posted: Tuesday, April 12, 2022

The variation in the frequency of EGFR and KRAS somatic mutations in lung cancer may be associated with genetic ancestry in patients from Latin America, according to study results presented as a Plenary Session at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract PL03). Matthew L. Meyerson, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues noted that their work dovetails with the larger body of research about variations in mutations associated with lung adenocarcinoma in distinct ancestry groups, which may be related to inherited factors.

In patients from Latin America, the authors explained, the frequency of somatic lung cancer EGFR mutations varies by country, with higher frequencies in Peru; intermediate frequencies in Mexico, Colombia, Costa Rica, and Brazil; and lower frequencies in Argentina. So, “to explore the relationship between the somatic genome in lung cancer and ethnicity-related germline risk, we performed cancer gene panel sequencing of DNA from [more than] 1,000 lung cancers from Mexico and Colombia, countries with significant population admixture,” they continued.

The team’s work revealed specific associations between ancestry and somatic lung cancer genomic alterations. They included tumor mutational burden and particular driver mutations in EGFR, KRAS, and STK11.

“We developed methods to infer ancestry from the tumor DNA sequence based on coverage of single nucleotide polymorphisms,” Dr. Meyerson and co-investigators stated. Among their findings was that “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, could underlie these disparities.” In the future, finding a germline locus or loci that affect the development of lung cancers with EGFR and/or KRAS mutations could help improve lung cancer prevention and screening processes for populations of Latin American origin, as well as for others, they concluded.

Disclosure: The study authors’ disclosure information can be found at abstractsonline.com.


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