Combined Effects of CYP1A1 MspI and GSTM1 Genetic Polymorphisms on Risk of Lung Cancer: an Updated Meta-analysis

Genetic polymorphisms of cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes might contribute to the variability in individual susceptibility to lung cancer, but the reported results from individual studies are not always consistent. We therefore conducted a meta-analysis to systematically estimate the associations between polymorphisms of these two genes and risk of lung cancer. Twenty-one studies with 8,926 subjects were finally enrolled into this study. Meta-analysis was performed by RevMan 5.2. Odds ratio (OR) and its 95 % confidence interval (CI) were calculated to evaluate the susceptibility to lung cancer. Compared with the wild-type homozygous genotype, significantly elevated risk of lung cancer were associated with variant CYP1A1 MspI (m1/m2 + m2/m2 vs. m1/m1: OR = 1.27, 95 % CI = 1.12-1.43, P < 0.001) and deletion of GSTM1 (null vs. present: OR = 1.26, 95 % CI = 1.13-1.40, P < 0.001). Both the two genetic polymorphisms were independently associated with the risk of lung cancer. The pooled OR of lung cancer for population with both CYP1A1 MspI and GSTM1 mutations (MspI m1/m2 or m2/m2 and GSTM1 null) was 1.62 (95 % CI 1.27-2.07, P < 0.001) when compared with those without any of the above mutations, which is higher than single genetic polymorphism. In the stratified analysis, significantly higher risks of lung cancer associated with above genetic polymorphisms were found only in Asian population. This meta-analysis suggests that the CYP1A1 MspI and GSTM1 polymorphisms correlate with increased lung cancer susceptibility independently, and that there is an interaction between the two genes. However, the associations vary in different ethnic populations.