Institute of Medical Genetics, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
Oncol Rep. 2011 Aug;26(2):479-85. doi: 10.3892/or.2011.1298. Epub 2011 May 10.
Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan® allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (p<0.001). None of the polymorphisms studied was associated with breast cancer risk. A significant interaction was observed between MnSOD 47T>C and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.
长期激素替代疗法（HRT）使用与乳腺癌风险增加之间的关系仍存在争议。雌激素代谢途径中功能相关的遗传变异可能改变外源性性激素的暴露，并影响绝经后乳腺癌的风险。我们研究了编码雌激素代谢途径关键蛋白的 4 个基因中的常见多态性与 HRT 使用持续时间及其与乳腺癌风险的相互作用。我们研究了 530 例乳腺癌病例和 270 例年龄和种族相同的病例对照研究中的绝经后妇女对照。通过邮寄问卷确定 HRT 使用持续时间。通过基于 PCR 的 RFLP 和 TaqMan®等位基因鉴别方法对 CYP1B1(rs1056836)、COMT(rs4680)、GSTP1(rs1695)和 MnSOD(rs4880)多态性进行基因分型。使用逻辑回归分析计算调整后的优势比和 95%置信区间。HRT 使用与乳腺癌风险降低显著相关（p<0.001）。研究的多态性均与乳腺癌风险无关。MnSOD 47T>C 与 HRT 使用之间观察到显著的交互作用（pinteraction=0.036）；与短期 HRT 使用相比，长期 HRT 使用与乳腺癌相关的风险在 MnSOD 47T>C 多态性野生型等位基因纯合的女性中降低，在至少有一种 MnSOD 47T>C 多态性变异等位基因的女性中增加。我们的结果表明，MnSOD 47T>C 多态性与长期 HRT 使用相互作用可能改变乳腺癌的风险。
