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目的探讨雌激素代谢通路相关基因CYP1A1、GSTT1、GSTM1与乳腺癌易感性的关系。方法采用聚合酶链反应(PCR)、限制性片段长度多态性(RFLP)及琼脂糖凝胶电泳法,对天津市360例正常女性和315例女性乳腺癌患者的CYP1A1、GSTT1、GSTM1基因及多态性进行检测,Logistic回归分析评估单基因、联合基因以及相关因素对乳腺癌的危险度。结果 CYP1A1基因、GSTT1基因、GSTM1基因在两组间分布频率有差异(χ2值分别为20.677,47.250,43.621,P=0.000)。基因型联合分析显示,随着携带危险基因型数目的增加,个体罹患乳腺癌的危险性增加(χ2=51.366,P=0.000)。多因素非条件Logistic回归分析结果显示,CYP1A1基因与体育锻炼、摄入肉类(每日多于150g)、摄入蔬菜(每日超过300g)的交互作用有统计学意义[OR(95%CI)分别为0.465(0.362～0.597)、1.559(1.344～1.808)、0.465(0.362～0.597)];GSTT1基因缺失、GSTM1基因缺失是乳腺癌的危险因素[OR(95%CI)分别为3.245(1.645～6.375)、2.462(1.818～3.334)],且GSTT1基因与体育锻炼、累计行经年数的交互作用有统计学意义[OR(95%CI)分别为1.546(1.113～2.147)、3.735(1.401～9.956)],GSTM1基因与哺乳期限、绝育手术的交互作用有统计学意义[OR(95%CI)分别为1.206(1.024～1.420)、1.690(1.353～2.111)]。结论雌激素代谢通路相关基因与乳腺癌发生有关,且其与雌激素暴露影响因素、生活方式等存在交互作用。
Objective To investigate the relationship between estrogen metabolic pathway related genes CYP1A1, GSTT1, GSTM1 and breast cancer susceptibility. Methods The CYP1A1, GSTT1 and GSTM1 genes in 360 normal women and 315 women with breast cancer in Tianjin were analyzed by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and agarose gel electrophoresis Polymorphisms were tested and Logistic regression analysis was used to assess the risk of breast cancer in single gene, combined gene and related factors. Results The distribution frequencies of CYP1A1, GSTT1 and GSTM1 genes were different between the two groups (χ2 = 20.677, 47.250, 43.621, P = 0.000). Genotypic analysis showed that the risk of developing breast cancer increased with the number of risk-bearing genotypes (χ 2 = 51.366, P = 0.000). Multivariate non-conditional logistic regression analysis showed that the interaction between CYP1A1 gene and physical activity, intake of meat (more than 150g daily) and intake of vegetables (more than 300g daily) was statistically significant [OR (95% CI ) Were 0.465 (0.362-0.597), 1.559 (1.344-1.808) and 0.465 (0.362-0.597), respectively. The deletion of GSTT1 gene and loss of GSTM1 gene were the risk factors for breast cancer (OR 95% CI: 3.245 ~ 6.375), 2.462 (1.818 ~ 3.334), respectively. The interaction between GSTT1 gene and physical exercise and accumulated years of operation was statistically significant (OR 95.95% CI 1.546 (1.113 2.147) 3.735 (1.401 9.956 )]. The interaction between GSTM1 gene and lactation duration and sterilization was statistically significant [OR (95% CI: 1.206 (1.024-1.420), 1.690 (1.353-2.1110)]. Conclusion The genes related to estrogen metabolism pathways are related to the occurrence of breast cancer, and their interaction with estrogen exposure factors, life style and so on.