Millikan R C, Pittman G S, Tse C K, Duell E, Newman B, Savitz D, Moorman P G, Boissy R J, Bell D A
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill 27599-7400, USA.
Carcinogenesis. 1998 Nov;19(11):1943-7. doi: 10.1093/carcin/19.11.1943.
Recent studies suggest that a polymorphism in catechol-O-methyltransferase (COMT) is associated with increased risk of breast cancer. Methylation by COMT is the principal pathway for inactivation of catechol estrogens, which are hypothesized to participate in estrogen-induced carcinogenesis. We examined the association of COMT genotype and breast cancer risk in a population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 654 cases and 642 controls, with approximately equal numbers of African-American and white women and women under the age of 50 and aged 50 or over. Contrary to previous reports, we did not observe an association between one or more copies of the low activity COMT allele (COMT-L) and breast cancer risk. Multivariate relative risks (RRs) were 0.8 (95% confidence interval: 0.6-1.1) for COMT-HL and 0.8 (0.6-1.1) for COMT-LL, compared with the COMT-HH genotype. RRs for COMT did not differ among African-American and white women and we did not observe strong modification of RR estimates by menopausal status, body mass index, physical activity or other covariates. Our results suggest that COMT genotype is not related to breast cancer risk.
近期研究表明，儿茶酚-O-甲基转移酶（COMT）基因多态性与乳腺癌风险增加相关。COMT介导的甲基化是儿茶酚雌激素失活的主要途径，据推测儿茶酚雌激素参与雌激素诱导的致癌过程。我们在北卡罗来纳州一项基于人群的浸润性乳腺癌病例对照研究中，检测了COMT基因型与乳腺癌风险之间的关联。研究人群包括654例病例和642例对照，非裔美国女性和白人女性、50岁以下女性和50岁及以上女性数量大致相等。与之前的报道相反，我们未观察到低活性COMT等位基因（COMT-L）的一个或多个拷贝与乳腺癌风险之间存在关联。与COMT-HH基因型相比，COMT-HL的多变量相对风险（RR）为0.8（95%置信区间：0.6-1.1），COMT-LL为0.8（0.6-1.1）。非裔美国女性和白人女性中COMT的RR无差异，并且我们未观察到绝经状态、体重指数、身体活动或其他协变量对RR估计值有显著影响。我们的结果表明，COMT基因型与乳腺癌风险无关。
