Lung Cancer Risk, Genetic Variation, and Air Pollution

Abstract

Large-scale multinational genome-wide association studies (GWAS) of the genetic variation associated with lung cancer initially found that the 5p15.33, 6p21.33, and 15q25 regions were associated with risk of lung cancer among smokers (Amos et al., 2008, Hung et al., 2008). Interestingly, unique regions including 10q25.2, 6q22.2 and 6p21.32 were associated with lung cancer risk in those who had never smoked (Lan et al., 2012), suggesting that the risk variants for non-smoking related lung cancer were distinct from those for smoking related lung cancer. Given that tobacco smoking is the leading risk factor for lung cancer, it stands to reason that lung cancer in those that abstain from tobacco use would have additional novel risk factors which might include genetics or environmental exposures. Some of the main non-tobacco exposures associated with lung cancer are household air pollution, radon, occupational exposures, and outdoor air pollution (Alberg and Samet, 2003). Among the a priori regions identified by Lan et al.'s GWAS of never smokers, significant gene–environment interactions with household air pollution (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04) were identified, thus suggesting that the risk of lung cancer associated with household air pollution exposure varied with the respective alleles for these regions. This study and other similar genetic studies provide evidence that the relationships between airborne exposures and genetic variation may contribute to lung cancer among non-smoking individuals.