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

• Published in: Respirology (Carlton, Vic.) Vol. 30; no. 4; pp. 317 - 325
• Main Authors: Chen, I‐Chieh, Chen, Yi‐Ming, Yang, Hui‐Wen, Tseng, Jeng‐Sen, Yang, Tsung‐Ying
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.04.2025; Wiley Subscription Services, Inc
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - epidemiology; Adenocarcinoma of Lung - etiology; Adenocarcinoma of Lung - genetics; Aged; Air pollution; Air Pollution - adverse effects; Air Pollution - statistics & numerical data; Case-Control Studies; Environmental Exposure - adverse effects; Female; Genetic Predisposition to Disease; Genetic Risk Score; Humans; lung adenocarcinoma; Lung cancer; Lung Neoplasms - epidemiology; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Male; Middle Aged; Multifactorial Inheritance; Particulate Matter - adverse effects; PM2.5; Pollution levels; polygenic risk score; Population studies; Precision medicine; Retrospective Studies; Risk Factors; Smoking; Smoking - adverse effects; Smoking - epidemiology; Taiwan - epidemiology; Taiwan; air pollution; polygenic risk score; PM2.5; lung adenocarcinoma; smoking
• ISSN: 1323-7799; 1440-1843; 1440-1843
• DOI: 10.1111/resp.70004

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. PRS (polygenic risk score) significantly predicted lung adenocarcinoma incidents in a dose‐dependent manner among never‐smokers. The results were consistent among participants exposed to different air pollution levels. High PM2.5 exposure was associated with a higher risk of lung adenocarcinoma among never‐smokers with low genetic risk.