CYP1A1 Polymorphisms and Risk of Lung Cancer in Non-Smoking Chinese Women: Influence of Environmental Tobacco Smoke Exposure and GSTM1/T1 Genetic Variation

Objective: We examined whether polymorphisms of CYP1A1, which plays a role in the metabolic activation of polycyclic aromatic hydrocarbons (PAHs), confer an increased risk of lung cancer in lifetime non-smoking Chinese women. Methods: A total of 126 incident lung cancer cases, of which 87.7% were pathologically confirmed, and 162 age-matched hospital controls were included. CYP1A1 MspI and$\text{Ile}^{462}\text{Val}$polymorphisms were genotyped and tested for association with this disease. Results: An elevated risk of lung cancer was observed among individuals with the MspI CC (OR = 1.7, 95% CI = 0.9-3.3) and$\text{Ile}^{462}\text{Val}$ValVal genotypes (OR = 2.8, 95% CI = 1.1-7.6). After stratifying by environmental tobacco smoke (ETS) exposure, the risk of lung cancer associated with both polymorphisms was higher among individuals with lower exposure to ETS, compared with those who reported at least weekly exposure. Individuals with the MspI CC genotype showed a two-fold higher risk of lung cancer if they were also null for either GSTM1 or T1 (OR = 2.3, 95%CI = 1.0-5.0 and OR = 2.7, 95% CI = 1.1-6.9, respectively, compared to other genotype combinations combined). Conclusions: CYP1A1 is a susceptibility gene for lung cancer among non-smoking Asian women and this association can be influenced by ETS exposure and genetic variation at GST genes.