Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States)

Objective: Cytochrome P450 1A1 plays a major role in the bioactivation of a number of tobacco procarcinogens. Much interest has focused on a polymorphism in exon 7 of the CYP1A1 gene which has been associated with a more inducible form of the enzyme. However, past results of its association with lung cancer have been inconsistent, especially in Caucasians. We carried out a pooled analysis of the data submitted to the Genetic Susceptibility to Environmental Carcinogens (GSEC) database to further investigate this association and, especially, to examine the modifying effects of smoking status and race. Methods: The data set used in this analysis included 11 studies and a total of 1950 cases and 2617 controls. Both fixed- and random-effects, meta-analysis models were used to investigate heterogeneity among studies. Because no clear heterogeneity was found, a pooled analysis was conducted using unconditional logistic regression. Results: The pooled odds ratio for subjects heterozygous and homozygous for the exon 7 polymorphism was 1.15 (95% confidence interval: 0.95-1.39) and 1.54 (95% CI: 0.97-1.46), respectively (p for gene-dosage effect: 0.03). This association was stronger for squamous cell carcinoma (SCC) than adenocarcinoma, and appeared to be stronger in Caucasians than Asians (p for interaction: 0.03). Statistically significant interactions were also detected for smoking status and sex, with the effect of the polymorphism being stronger in never-smokers and in females. Conclusions: The present data suggest that the CYP1A1 exon 7 polymorphism may confer an increased risk of lung cancer, particularly of SCC, and especially in never-smokers and in women. These interactions need to be confirmed when additional studies are available for pooling.