CYP17、CYP19、SULT1A1基因多态性与汉族女性乳腺癌易感性的研究

Study on the relationship between polymorphisms of genes (CYP17, CYP19 and SULT1A1) and susceptibility to breast cancer in Chinese women

目的探讨雌激素代谢酶CYP17、CYP19、SULT1A1基因多态性与女性乳腺癌易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性及短臂重复多态性方法,检测213例乳腺癌患者和430名正常对照CYP17、CYP19、SULT1A1基因多态性分布;应用logistic回归等方法分析单个基因、多个基因联合及雌激素暴露因素对乳腺癌的危险度。结果 CYP17变异等位基因A2病例组的频率为49．8％,对照组为49．1％,差异无统计学意义(P>0．05);SULT1A1变异等位基因His 病例组的频率为13．6％,高于对照组的频率9．5％,差异有统计学意义(P=0．03);CYP19(TTTA)10等位基因病例组的频率为12．4％,对照组为8．2％(P=0．02);多基因模型分析显示,携带多个高危险基因显著增加患乳腺癌的危险性(趋势P=0．05);多因素分析显示,携带SULT1A1 His及CYP19 (TTTA)10等位基因与乳腺癌危险性相关;高雌激素暴露因素如累计行经年数长、初潮年龄早以及体重指数、腰臀比高等均为乳腺癌的危险因素。结论参与雌激素合成与代谢的多个酶基因多态性与乳腺癌的发生有关。

Objective To investigate the relationship between polymorphisms of genes（CYP17, CYP19 and SULT1A1） involved in estrogen metabolism and susceptibility to breast cancer in Chinese women. Methods A case-control study was performed. PCR-base restriction fragment length polymorphism（PCR-RFLP） and short tandem repeat polymorphism（STRP） assays were used to detect the polymorphism distribution of CYP17, CYP19 and SULT1A1 in 213 breast cancer cases and 430 matched controls, Logistic regression analyses were used to determine the OR, multivariate adjusted OR and 95 % CI of each and all three genes and estrogen exposure factors on the risk of breast cancer. Relationship between polymorphisms and clinic-patbological features was also assessed. Results The frequency of A2 allele of CYP17 was 49.8% in cases and 49.1% in controls （P 〉 0.05）. The frequency His allele of SULT1A1 in cases（ 13.6 % ） was significant higher than that of controls（9.5 % ） （ P = 0.03）. There was also significant difference in the frequencies of（TTTA）10 allele CYP19 which was 12.4% in cases and 8.2 % in controls（ P-0.02）. Muhigenic model indicated that there was an increased risk of breast cancer with more numbers of high-risk genotypes in a dose-response effect （trend P=0.05）. Data from multivariate analysis showed that the allele of SULT1A1 His and CYP19 （TTTA）I0 was positively associated with the risk of breast cancer. Other well-established risk factors as higher estrogen exposure including total years of menstrual, early menarche ete, and women with a higher BMI and WHR were all served as independent risks. Conclusion This study indicated that the polymorphisms of estrogen- metabolizing genes were related to breast cancer.