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目的运用多因子降维法(MDR)分析代谢酶易感基因多态性对乳腺癌患病风险的交互作用,并评价MDR模型的具体应用。方法采用配对病例对照研究,共收集按年龄和绝经状态匹配的病例对照对子78对。用PCR-RFLP和多重PCR法分别检测调查对象CYP1A1 MspⅠ、GSTM1以及GSTT1易感基因类型;运用MDR法分析基因-基因交互作用模型;并构建最优的乳腺癌的环境及基因的logistic模型。结果有统计学意义的最佳交互作用模型是CYP1A1 MspⅠ突变基因型与GSTT1 null基因型的联合作用(sign检验,P=0.05),该模型的检验样本平衡准确度为0.5920,交叉效度一致性的结果为10/10。根据MDR分析结果构建的条件logistic回归模型结果显示,被动吸烟、未足月产数以及GSTT1 null基因型和CYP1A1 MspⅠ突变基因型的交互项是乳腺癌的危险因素,ORs分别为12.234(1.7459~85.7279)、4.554(1.3250~15.6507)和9.597(1.5783~58.3599)。结论将MDR法与参数估计的分析方法相结合,是对肿瘤等慢性非传染性疾病的基因-基因或基因-环境多重病因效应估计的有益尝试。CYP1A1 MSPⅠ突变基因型及GSTT1缺失基因型可能协同干扰雌激素代谢的过程,从而增加了乳腺癌的发生风险。
Objective To analyze the interaction of metabolic enzyme susceptibility gene polymorphisms on the risk of breast cancer using multiple factor reduction (MDR) and evaluate the specific application of MDR model. Methods Paired case-control studies were conducted. A total of 78 pairs of case-control pairs matched by age and menopause were collected. The CYP1A1 MspI, GSTM1, and GSTT1 susceptibility gene types were investigated by PCR-RFLP and multiplex PCR. The gene-gene interaction model was analyzed using the MDR method, and an optimal logistic model of the environment and genes of breast cancer was constructed. Results The statistically significant optimal interaction model was the combined effect of the CYP1A1 MspI mutant genotype and the GSTT1 null genotype (signal test, P=0.05). The accuracy of the test sample for this model was 0.5920, and the cross-validity was consistent. The result is 10/10. According to the results of conditional logistic regression model constructed from MDR analysis results, passive smoking, incomplete monthly production, and interactions between GSTT1 null genotype and CYP1A1 MspI mutant genotype were risk factors for breast cancer, ORs were 12.234 (1.7459 to 85.7279). ), 4.554 (1.3250~15.6507) and 9.597 (1.5783~58.3599). Conclusion Combining the MDR method with the parameter estimation analysis method is a useful attempt to estimate the gene-gene or gene-environment multiple etiological effects of tumors and other chronic non-infectious diseases. CYP1A1 MSPI mutant genotype and GSTT1 deletion genotype may coordinate the process of estrogen metabolism, thereby increasing the risk of breast cancer.