Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk: a meta-analysis

Abstract

Cytochrome P450 1B1 (CYP1B1) is a P450 enzyme implicated in the metabolism of exogenous and endogenous substrates. The metabolism of polycyclic aromatic hydrocarbons and other procarcinogens through CYP1B1 may well lead to their activation. Apart from the extensively studied Val432Leu polymorphism, three single nucleotide polymorphisms in CYP1B1 have been studied concerning their potential implication in terms of breast cancer risk: Arg48Gly, Ala119Ser and Asn453Ser. This meta-analysis aims to examine whether the three aforementioned polymorphisms are associated with breast cancer risk. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to December 2009. Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321 cases and 13,379 controls); 11 studies were eligible for Ala119Ser (10,715 cases and 11,678 controls); 12 cases were eligible regarding Asn453Ser (11,630 cases and 14,053 controls). Pooled odds ratios (OR) were appropriately derived form fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg equilibrium was performed. Concerning Arg48Gly, the pooled ORs (95% CI) were 0.933 (0.808-1.078) for heterozygous and 0.819 (0.610-1.100) for homozygous Gly subjects. Regarding Ala119Ser, the pooled ORs were 0.992 (0.896-1.097) for heterozygous and 0.935 (0.729-1.198) for homozygous Ser subjects. With respect to Asn453Ser, the pooled ORs were 0.961 (0.906-1.019) for heterozygous and 0.984 (0.846-1.144) for homozygous Ser subjects. In conclusion, this meta-analysis suggests that CYP1B1 Arg48Gly, Ala119Ser and Asn453Ser polymorphisms are not associated with breast cancer risk. Studies on Chinese populations are needed, to elucidate race-specific effects on East Asian populations, if any.