Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status

We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the EGFR gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared with EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (odds ratio = 8.63, 95% confidence interval: 5.67–13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (odds ratio = 3.50, 95% confidence interval: 2.44–5.00) (p-heterogeneity = 3.66 × 10−3). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.