Association between the CYP1A1 A2455G polymorphism and risk of cancer: evidence from 272 case-control studies.

ABSTRACT

A2455G is a common polymorphism in CYP1A1, showing differences in its biological functions. Case-control studies have been performed to elucidate the role of A2455G in cancer; however, the results are conflicting and heterogeneous. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and A2455G (64,593 cases and 91,056 controls from 272 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model, odds ration [OR] = 1.19, 95% confidence interval [CI] = 1.13-1.25; recessive model OR = 1.41, 95% CI = 1.29-1.54; additive model OR = 1.49, 95% CI = 1.35-1.65) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of breast cancer, colorectal cancer, esophageal cancer, hepatocellular cancer, head and neck cancer, leukemia, lung cancer, and prostate cancer, but these associations vary in different ethnic populations. In summary, this meta-analysis suggests the participation of A2455G in the susceptibility for some cancers, such as breast cancer, colorectal cancer, lung cancer, and so on. Moreover, ethnicity, histological type of cancer, and smokers seem to contribute to varying expressions of the A2455G on some cancers risk. In addition, our work also points out the importance of new studies for A2455G polymorphism in some cancer types, such as gallbladder cancer, Indians of breast cancer, and Caucasians of ovarians, because these cancer types had high heterogeneity in this meta-analysis (I(2) > 75%).