Association of CYP1B1 Leu432Val Polymorphism and Lung Cancer Risk: An Updated Meta-Analysis

Abstract

Cytochrome P4501B1 (CYP1B1) a phase I enzyme, is involved in the activation of a broad spectrum of procarcinogens. Impacts on the catalytic activity of the CYP1B1 enzyme, as well as an association of the Leu432Val polymorphism with the risk of lung cancer, have been described; however, the results remain controversial. We conducted a meta-analysis of all available studies to clarify the effects of the Leu432Val polymorphism on lung cancer risks basing on 2,543 lung cancer cases and 3,304 controls from ten separate comparisons. We also performed subgroup analyses by ethnicity (categorized as Caucasian, Asian and African-American), gender, smoking status ,and histological type. A pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the strength of the association. A significantly increased risk was found in our meta-analysis in the overall population (Val/Val vs. Leu/Leu: OR = 1.371, 95% CI 1.137-1.652, P = 0.001). In subgroup analysis, significant associations with lung cancer susceptibility were also found in Caucasians (Val/Val vs. Leu/Leu: OR = 1.312, 95% CI 1.075-1.602, P = 0.008), females (Val/Val vs. Leu/Leu: OR = 1.472, 95% CI 1.097-1.976, P = 0.010), and smokers (dominant model Leu/Val + Val/Val vs. Leu/Leu: OR = 1.257, 95% CI 1.016-1.554, P = 0.035). Null results were noted in the subgroup analysis by histological type under different genetic models. Our results suggest that the CYP1B1 Leu432Val polymorphism acts as a risk factor for the carcinogenesis of lung cancer.