School of Medicine, National University of Athens, Athens, Greece.
Breast Cancer Res Treat. 2010 Jul;122(2):545-51. doi: 10.1007/s10549-009-0728-z. Epub 2010 Jan 7.
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.
细胞色素 P450 1B1（CYP1B1）是一种 P450 酶，参与外源性和内源性底物的代谢。多环芳烃和其他前致癌物质通过 CYP1B1 的代谢可能导致它们的激活。除了广泛研究的 Val432Leu 多态性外，CYP1B1 中的三个单核苷酸多态性已被研究，以探讨其在乳腺癌风险方面的潜在意义：Arg48Gly、Ala119Ser 和 Asn453Ser。本荟萃分析旨在研究上述三种多态性是否与乳腺癌风险相关。通过搜索 MEDLINE 书目数据库，确定了截至 2009 年 12 月的合格文章。关于 Arg48Gly 多态性，有 10 项研究合格（11321 例病例和 13379 例对照）；11 项研究合格（10715 例病例和 11678 例对照）；有 12 项研究合格（11630 例病例和 14053 例对照）。从固定效应或随机效应模型中适当得出了合并优势比（OR）。对对照组基因型频率明显偏离哈迪-温伯格平衡的研究进行了敏感性分析。关于 Arg48Gly，杂合子的合并 OR（95%CI）为 0.933（0.808-1.078），纯合子 Gly 为 0.819（0.610-1.100）。对于 Ala119Ser，杂合子的合并 OR 为 0.992（0.896-1.097），纯合子 Ser 为 0.935（0.729-1.198）。对于 Asn453Ser，杂合子的合并 OR 为 0.961（0.906-1.019），纯合子 Ser 为 0.984（0.846-1.144）。总之，本荟萃分析表明，CYP1B1 Arg48Gly、Ala119Ser 和 Asn453Ser 多态性与乳腺癌风险无关。需要进行针对中国人群的研究，以阐明在东亚人群中是否存在种族特异性影响。
