雌激素代谢基因COMT和CYP17单核苷酸多态与女性乳腺癌风险的关系  

Relation between single nucleotide polymorphism in estrogen-metabolizing genes COMT,CYP17 and breast cancer risk among Chinese women

作　　者：谭文[1] 齐军[2] 邢德印[1] 缪小平[1] 潘凯枫[3] 张联[3] 林东昕[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院病因及癌变研究室,北京100021 [2]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院检验科,北京100021 [3]北京大学临床肿瘤学院北京市肿瘤防治研究所

出　　处：《中华肿瘤杂志》2003年第5期453-456,共4页Chinese Journal of Oncology

基　　金：国家杰出青年科学基金资助项目 (3 982 5 12 2 ) ;北京市自然科学基金资助项目 (70 13 0 3 5 )

摘　　要：目的　研究参与雌激素合成的细胞色素P4 5 0c17(CYP17)和雌激素代谢解毒的儿茶酚 O 甲基转移酶 (COMT )基因多态与乳腺癌发生的关系。方法　以聚合酶链反应和限制性片段长度多态方法 ,对 2 5 0例乳腺癌患者和 2 5 0例正常对照者的COMT基因第 4外显子第 15 8位密码子G/A(Val/Met)多态和CYP17基因启动子区 - 1931T/C多态进行分析。以logistic回归模型计算各种基因型的乳腺癌风险 (OR)及其 95 %可信区限 (95 %CI)。结果　乳腺癌患者的COMTMet/Met基因型频率为 10 .4 % ,显著高于对照组的 5 .2 % (P =0 .0 3)。多因素分析显示 ,COMTMet/Met基因型患乳腺癌的风险比Val/Val或Val/Met基因型高 2 .1倍 (95 %CI为 1.1～ 4 .5 )。分层分析显示 ,COMTMet/Met基因型主要增加绝经前女性患乳腺癌的风险 (OR 4 .1,95 %CI为 1.2～ 17.3) ,而不增加绝经后女性患乳腺癌的风险 (OR 1.3,95 %CI为 0 .5～ 3.5 ) ,提示该基因多态对乳腺癌风险的影响与雌激素水平有关。CYP17基因型频率在病例和对照组中的分布差异无显著性 (P =0 .83)。结论　COMT基因单核苷酸多态与乳腺癌易感性相关 ,Met/Met基因型增加乳腺癌风险 ,而CYP17基因多态与中国女性乳腺癌风险无相关性。Objective To test the hypothesis whether polymorphism in estrogen-metabolizing genes, COMT and CYP17, impacts on the risk of breast cancer among Chinese women. Methods COMT (Val158Met) and CYP17 (T1931C) polymorphisms were detected by PCR-based restriction fragment length polymorphism analysis in 250 breast cancer patients and 250 frequency-matched normal controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression. Results COMT Met/Met genotype was found in 10.4% of breast cancer patients, which was significantly higher (P= 0.03) than that in controls (5.2%). Women with Met/Met genotype showed 2-fold increased risk for breast cancer (adjusted OR 2.1, 95%CI 1.1- 4.5 ) compared with those with Val/Val or Val/Met genotypes. Stratified analysis showed that the elevated risk of breast cancer, associating with the COMT Met/Met genotype, was evident only among premenopausal women (adjusted OR 4.1,95%CI 1.2-17.3) but not among postmenopausal women (adjusted OR 1.3,95%CI 0.5- 3.5 ). There was no significant difference in the distribution of CYP17 genotypes between breast cancer patients and the control subjects (P=0.83). Conclusion The allele encoding for low activity COMT, but not CYP17, may be a genetic risk factor for breast cancer among Chinese women.

关 键 词：雌激素 代谢基因 COMT CYP17单核苷酸多态 女性 乳腺癌 肿瘤医院 病因 

分 类 号：R737.9[医药卫生—肿瘤]