Interplay of Polygenic Risk Score, Smoking Statuses, and Air Pollution on Lung Adenocarcinoma Risk in a Taiwanese Population
ABSTRACT
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 PM2.5 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 PM2.5 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 PM2.5 exposure (4.97 [95% CI 3.10–7.97], p < 0.001). There was no significant impact of PM2.5 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.
