Geographic Variation in EGFR Mutation Frequency in Lung Adenocarcinoma May Be Explained by Interethnic Genetic Variation

Our understanding of the etiology of EGFR-mutant lung cancer remains incomplete. One persistent finding in the literature is the geographic variation in the frequency of EGFR mutations in lung adenocarcinoma. We investigated the association between two biomarkers of East Asian ancestry, the genetic polymorphisms ectodysplasin A receptor gene (EDAR) V370A and ATP binding cassette subfamily C member 11 gene (ABCC11) G180A, and the frequency of EGFR mutations in patients with lung adenocarcinoma in a range of countries. The Pearson's linear correlation between the frequency of EGFR mutations and the EDAR polymorphism was 0.92 (p <2.2 × 10-10), and for the ABCC11 polymorphism it was 0.72 (p <1.6 × 10-4). These results suggest that the variation in the measured frequency of EGFR mutations in lung adenocarcinoma can be explained, at least in part, by interethnic genetic variation. To improve our understanding of this disease, studies exploring the genetic polymorphism(s) that cause these interethnic differences, as well as the mechanisms of actions through which they work, are warranted.