Cytochrome P4501B1 and catechol-O-methyltransferase polymorphisms and endometrial cancer susceptibility
Cytochrome P4501B1 and catechol-O-methyltransferase polymorphisms and endometrial cancer susceptibility
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DOI：
10.1093/carcin/bgh039
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发表时间：
2004-04-01
期刊：
影响因子：
4.7
通讯作者：
De Vivo, I
中科院分区：
文献类型：
--
作者：
McGrath, M;Hankinson, SE;De Vivo, I
雌激素的产生和代谢在子宫内膜癌的发生发展中起着重要作用。细胞色素P450 1B 1（CYP 1B 1）和儿茶酚-O-甲基转移酶（COMT）是雌激素代谢途径中的两个关键酶，分别参与雌二醇的羟基化和结合。我们评估了CYP 1B 1 Leu 432 Val和CYP 1B 1 Asn 453 Ser多态性和COMT Val 158 Met多态性与浸润性子宫内膜癌风险之间的关系，这是一项嵌套在护士健康研究中的病例对照研究（n = 222例，666例对照）。我们还评估了体重指数（BMI）、绝经后激素（PMH）使用和吸烟是否改变了CYP 1B 1和COMT基因型与子宫内膜癌风险的相关性。条件Logistic回归用于计算校正的比值比（OR）和95%置信区间（CI），以量化至少有一个变异等位基因的受试者与野生型等位基因纯合子受试者相比患子宫内膜癌的风险。CYP 1B 1 Ser等位基因携带者发生子宫内膜癌的风险显著降低（OR = 0.62; 95%CI，0.42-0.91）; CYP 1B 1瓦尔等位基因与子宫内膜癌风险之间无显著相关性（OR = 1.10; 95%CI，0.75-1.59）。与COMT瓦尔/瓦尔野生型基因型相比，COMT瓦尔/Met或COMT Met/Met基因型妇女患子宫内膜癌的校正OR为0.96（95%CI为0.65-1.43）。我们没有观察到BMI、PMH使用和吸烟对CYP 1B 1和COMT基因型的任何影响。我们的数据表明，CYP 1B 1 Ser等位基因可能通过改变儿茶酚雌激素的产生来降低子宫内膜癌的风险。然而，需要进一步的研究来阐明CYP 1B 1在子宫内膜癌中的作用。
Estrogen production and metabolism play critical roles in the development and pathogenesis of endometrial carcinoma. Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are two key enzymes in the estrogen metabolism pathway that result in the hydroxylation and conjugation of estradiol, respectively. We evaluated the association between the CYP1B1 Leu432Val and CYP1B1 Asn453Ser polymorphisms and the COMT Val158Met polymorphism and invasive endometrial cancer risk in a case-control study nested within the Nurses' Health Study (n = 222 cases, 666 controls). We also evaluated whether body mass index (BMI), postmenopausal hormone (PMH) use and cigarette smoking modified the associations of the CYP1B1 and COMT genotypes and endometrial cancer risk. Conditional logistic regression was used to calculate the adjusted odds ratios (OR) and 95% confidence intervals (CI) to quantify the risk of endometrial cancer among subjects who had at least one variant allele compared with subjects who were homozygous for the wild-type allele. Carriers of the CYP1B1 Ser allele had a statistically significant decreased risk of endometrial cancer (OR = 0.62; 95% CI, 0.42-0.91); there was no significant association between the CYP1B1 Val allele and endometrial cancer risk (OR = 1.10; 95% CI, 0.75-1.59). Compared with the COMT Val/Val wildtype genotype, the adjusted OR of endometrial cancer for women with the COMT Val/Met or COMT Met/Met genotype was 0.96 (95% CI, 0.65-1.43). We did not observe any effect modification by BMI, PMH use and cigarette smoking for the CYP1B1 and COMT genotypes. Our data suggest, that the CYP1B1 Ser allele may decrease endometrial cancer risk by altering the production of catechol estrogens. However, further studies are warranted to elucidate the role of CYP1B1 in endometrial cancer.