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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 the polymorphisms of estrogen metabolizing enzymes CYP17, CYP19 and SULT1A1 and the susceptibility of female breast cancer. Methods Polymorphisms of CYP17, CYP19 and SULT1A1 in 213 cases of breast cancer and 430 normal controls were detected by polymerase chain reaction-restriction fragment length polymorphism and short-arm repeat polymorphism. Logistic regression Analysis of individual genes, multiple gene combinations and estrogen exposure factors on the risk of breast cancer. Results The CYP17 variant allele frequency was 49.8% in A2 case group and 49.1% in control group (P> 0.05). The frequency of SULT1A1 variant allele His case group was 13 .6%, higher than that of the control group 9.5%, the difference was statistically significant (P = 0.03); CYP19 (TTTA) 10 allele case frequency was 12.4%, the control group was 8 .2% (P = 0.02). Multiple gene model analysis showed that carrying multiple high-risk genes significantly increased the risk of breast cancer (trend P = 0.05). Multivariate analysis showed that carrying SULT1A1 His and CYP19 (TTTA) 10 alleles and breast cancer risk; high estrogen exposure factors such as accumulated long years of experience, early menarche and body mass index, high waist-hip ratio are risk factors for breast cancer. Conclusion The polymorphisms of multiple enzymes involved in estrogen synthesis and metabolism are related to the occurrence of breast cancer.