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目的研究有机氯农药二氯二苯三氯乙烷(DDT)类物质暴露及细胞色素P4501A1m2突变基因型对女性乳腺癌患病风险的交互作用。方法运用病例对照研究方法,自2003年12月起至2004年9月止,收集组织病理学确诊乳腺癌的女性病例104例,社区来源的健康女性对照154名。采用问卷调查方法获取病例和对照乳腺癌相关危险因素的信息;用气相色谱-电子捕获(GC-ECD)方法检测血清样品中对,对-二氯二苯三氯乙烷(p,p’-DDT)、对,对-二氯二苯三氯乙烯(p,p’-DDE)的含量;用特异性聚合酶链反应(AS-PCR)法检测CYP1A1m2突变型基因;用logistic回归模型分析DDT类有机氯物质血清含量及CYP1A1m2突变基因型与乳腺癌患病风险的相对危险度(OR),以及二者的联合作用。结果病例和对照两组血清中的DDT的含量分别是(36.90±79.41)ng/ml和(50.60±150.70)ng/ml;DDE的含量分别是(7.43±11.10)ng/ml和(8.96±11.30)ng/ml,几何均数检验,两组间差异无统计学意义(P>0.05);CYP1A1m2型突变纯合型基因型(Val/Val)的调整OR=2.61,95%CI:1.00~6.80;绝经前乳腺癌病例与对照组中,携带Val突变基因型且DDT高暴露的OR=4.35,95%CI:1.140~16.950,参照等级是Ile/Ile野生纯合型基因且DDT低暴露。结论CYP1A1m2突变型基因型可能与乳腺癌有关,DDT暴露可能增加携带CYP1A1易感基因型的绝经前女性患乳腺癌的风险。
Objective To study the interaction between organochlorine pesticides (DDTs) and the cytochrome P4501A1m2 genotype on the risk of breast cancer in women. Methods A case-control study was conducted. From December 2003 to September 2004, 104 cases of histopathologically confirmed breast cancer and 154 healthy women of community origin were collected. The information of risk factors related to breast cancer was obtained by questionnaire method. The contents of p, p-dichlorodibenzo-trichloroethane (p, p’- (P, p’-DDE) were determined by polymerase chain reaction (PCR-RFLP). The CYP1A1m2 mutant gene was detected by specific polymerase chain reaction (AS-PCR) The serum levels of organochlorine-like substances and the relative risk (OR) of the CYP1A1m2 mutant genotypes and the risk of breast cancer, as well as their combined effects. Results The serum levels of DDT in the two groups were (36.90 ± 79.41) ng / ml and (50.60 ± 150.70) ng / ml, respectively. The contents of DDE were (7.43 ± 11.10) ng / ml and (P> 0.05). The adjusted OR of CYP1A1m2 homozygous genotype (Val / Val) was 2.61, 95% CI: 1.00-6.80, and the geometric mean test showed no significant difference between the two groups . In premenopausal women with breast cancer and controls, the odds ratio (OR) was 4.35,95% CI: 1.140 to 16.950 with Val mutation genotypes and high DDT exposure. The reference grade was Ile / Ile wild homozygous with low DDT exposure. Conclusion CYP1A1m2 mutant genotype may be associated with breast cancer. DDT exposure may increase the risk of breast cancer in premenopausal women with CYP1A1 susceptibility.