Greater lung cancer polygenic risk score in higher air pollution areas linked to greater rate of lung adenocarcinoma: a single-centre study in East Asia.

Background: Lung cancer, a leading cause of cancer deaths, is influenced by smoking, air pollution and genetic factors. This study investigated the association between lung cancer polygenic risk score (PRS) and air pollution in lung adenocarcinoma (LUAD) cases in East Asia.

Methods: This Taiwanese case-control study included 57 257 participants, of whom 1059 were diagnosed with lung cancer and 857 had LUAD. Excluding individuals with missing PRS data, the final study group comprised 648 LUAD patients and 6480 age- and gender-matched controls. Logistic regression models were employed to assess the association between PRS and LUAD risk, and interaction effects between PRS and particulate matter (PM2.5/PM10) exposure were evaluated.

Results: PGS000070 demonstrated an OR of 2.796 (95% CI 2.236 to 3.497, p<0.001), while PGS000392 exhibited an OR of 1.938 (95% CI 1.559 to 2.409, p<0.001). Higher PM exposure increased LUAD risk among individuals in the highest quartile (Q4) of both PRSs compared with the lowest quartile (Q1). In the smoking subgroup, individuals in Q4 for PGS000070 showed significantly heightened LUAD risk when exposed to higher PM2.5 and PM10 levels, with ORs of 4.08 (p<0.0001) and 2.897 (p<0.0001), respectively. However, the interaction effect of PRS (PGS000070 and PGS000392) and PM exposure on LUAD risk was not statistically significant.

Conclusion: This hospital-based study indicated that LUAD patients had higher PRSs and greater exposure to PM. However, the interaction effect between PRS (PGS000070 and PGS000392) and PM exposure on LUAD risk was not statistically significant, suggesting these factors act independently. The accumulation of air pollution did not show a gradual increase in LUAD risk. Notably, the association between PRS and air pollution was more pronounced in the smoking subgroup for PGS000070 but not for PGS000392.