Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta-analysis

Abstract

Cytochrome P450s are enzymes which catalyze Phase-I metabolism reactions; cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family and participates in the metabolism of a vast number of xenobiotics, as well as endogenous substrates. Four single nucleotide polymorphisms in CYP1A1 have been studied concerning their potential implication in terms of breast cancer risk: T3801C, T3205C, A2455G (Ile462Val), and C2453A (Thr461Asp); controversy exists regarding their role. This meta-analysis aims to examine whether the four aforementioned polymorphisms are associated with breast cancer risk. Separate analyses were performed on Caucasian, Chinese, and African populations, as well as on premenopausal and postmenopausal women. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to October 2009. Concerning T3801C, 32 studies were eligible (11,909 cases and 16,179 controls), 29 studies (12,257 cases and 20,379 controls) were eligible for A2455G, 11 studies (7,189 cases and 8,491 controls) were eligible for C2453A, and eight studies were eligible for T3205C (1,378 cases and 1,642 controls). Pooled odds ratios (OR) were appropriately derived from fixed- or random-effect models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg equilibrium was performed. Homozygous subjects of Caucasian origin carrying the A2455G G allele exhibited elevated breast cancer risk (pooled OR = 2.185, 95% CI 1.253-3.808, fixed effects), whereas heterozygous carriers did not (pooled OR = 1.062, 95% CI 0.852-1.323, random effects). A2455G polymorphism status was not associated with breast cancer risk in Chinese subjects or specifically in premenopausal/postmenopausal women. T3801C, T3205C, and C2453A status were not associated with breast cancer risk at any analysis. In conclusion, this meta-analysis points to the A2455G G allele as a risk factor for breast cancer among Caucasian subjects. On the contrary, T3801C, T3205C, and C2453A status does not seem capable of modifying breast cancer risk.