Interplay of Polygenic Risk Score, Smoking Statuses, and Air Pollution on Lung Adenocarcinoma Risk in a Taiwanese Population.

Background and objective: We determined the impact of genetic susceptibility and its interaction with smoking and air pollution on the risk of developing lung adenocarcinoma.

Methods: This retrospective case-control study utilised data from Taiwan Precision Medicine Initiative (TPMI) project conducted between June 2019 and November 2022. The study population consisted of lung adenocarcinoma patients and 1:4 age-, gender-, and index year-matched non-lung cancer controls. We analysed polygenic risk scores (PRS), smoking status, as well as PM_2.5 and PM₁₀ exposures.

Results: A total of 681 lung adenocarcinoma patients and 2724 non-lung cancer participants were included. PRS was significantly higher among lung adenocarcinoma patients than controls (p < 0.001). Overall, a higher PRS was associated with a higher risk of lung adenocarcinoma. A high PM_2.5 exposure was associated with a higher risk of lung adenocarcinoma (OR 1.88 [95% CI 1.12-3.14], p = 0.0163) among never-smokers with low genetic risk. Never-smokers with a higher genetic risk were associated with a higher OR for lung adenocarcinoma with the highest OR among Q4 participants with high PM_2.5 exposure (4.97 [95% CI 3.10-7.97], p < 0.001). There was no significant impact of PM_2.5 exposure among individuals with higher genetic risks. Similar phenomena were observed in the PM₁₀ analyses. There were no significant correlations of PRS with risk of lung adenocarcinoma among smokers.

Conclusion: PRS significantly predicted lung adenocarcinoma incident cases in a dose-dependent manner among never-smokers. The PRS effect was not noted in smokers. The results were consistent among participants exposed to different air pollution levels.