Association between self-reported environmental tobacco smoke exposure and lung cancer:: Modification by GSTP1 polymorphism

Environmental Tobacco Smoke (ETS) exposure has been associated with lung cancer risk. ETS is composed of emissions from cigarette smoke and contains a higher concentration of tobacco smoke carcinogens than mainstream smoke. Polymorphisms in genes that metabolize tobacco smoke carcinogens have been studied as effect modifiers of the association between active smoking and lung cancer risk. GSTPI is a polymorphic gene that encodes for GST pi, a detoxification enzyme and has a high expression in the lung. We investigated the association between ETS and lung cancer risk and the modification of this association by the GSTPI polymorphism. Using a case-control design, individuals were genotyped for GSTPI using PCR-RFLP techniques. All analyses were carried out using multiple logistic regression. The association between ETS exposure and lung cancer risk was evaluated in different strata based on smoking habits to evaluate the consistency of results. The effect of the GSTPI polymorphisms on lung cancer risk was evaluated by considering the joint effect of having both an ETS exposure and the GSTPI GG genotype compared to the absence of ETS exposure and the GSTPI AA genotype as a reference group as well as doing stratified analysis by genotype. ETS exposure was associated consistently with higher lung cancer risk in all the strata considered. The adjusted odds ratios (AOR) evaluating the association between ETS and lung cancer risk for the different strata were: nonsmokers (Cases/Controls 66/413; AOR = 1.38; 95% CI = 0.78-2.43), ex-smokers (Cases/Controls 560/527; AOR = 1.66; 95% CI = 1.22-2.25), current smokers (Cases/Controls 415/219; AOR = 1.56; 95% CI = 1.00-2.41). The AORs for ex-smokers and light smoking subgroups were: ex-smokers who quit for 19 years or more (Cases/Controls 144/244; AOR = 2.64; 95% Cl = 1.55-4.50), ex-smokers who quit for 10-19 years (Cases/Controls 141/128; AOR = 1.16; 95% CI = 0.66-2.04), ex-smokers who quit for 10 years or less (Cases/Controls 247/122; AOR = 1.45; 95% CI = 0.83-2.55) and participants who had <15 packyears and nonsmokers combined (Cases/Controls 143/640; AOR = 1.52; 95% CI = 1.02-2.28). Among those with the GSTPI GG genotype the ETS-lung cancer risk association was greater than those with the GSTPI AA genotype: nonsmokers (GSTPI GG AOR = 7.84; 95% Cl = 0.80-76.68; GSTPI AA AOR = 1.15; 95% CI 0.46-2.90), ex-smokers (GSTPI GG AOR = 2.32; 95% CI 0.90-5.96; GSTPI AA AOR = 2.15; 95% CI = 1.34-3.44), current smokers (GSTPI GG AOR = 1.75; 95% CI = 0.42-7.32; GSTPI AA AOR = 1.32; 95% CI = 0.67-2.58) and participants who had < 15 packyears and nonsmokers (GSTPI GG AOR = 1.93; 95% CI = 034-6.97; GSTPI AA AOR = 1.58; 95% CI = 0.83-3.01). We found that ETS exposure is associated with higher lung cancer risk. Furthermore, the presence of the GSTPI GG genotype appears to enhance the magnitude of the association between ETS exposure and lung cancer. Larger studies will be needed to confirm these preliminary findings. (C) 2003 Wiley-Liss, Inc.