血清有机氯农药DDT暴露、CYP1A1基因多态性与乳腺癌患病风险的病例对照研究

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。

Study on serum organochlorines pesticides (DDTs) level,CYP1A1 genetic polymorphismand risk of breast cancer :a case control study

OBJECTIVE: To study the potential effect of gene-environment interaction between CYP1A1 and serum dichlorodiphenyldichloroethane (DDT) levels on the risk of breast cancer in women, in China. METHODS: A case-control study was conducted. From Dec. 2003 to Sep. 2004, 104 women with histologically confirmed breast cancers and 154 noncancerous controls from a community were enrolled in this study. Risk factors information of breast cancer was investigated by a questionnaire. Serum p, p'-dichlorodiphenyldichloroethane (p, p'-DDT) and 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels were tested by GC-ECD. CYP1A1 m2 gene type was tested by allele special-PCR method. RESULTS: Serum DDT levels of case and control were (36.90 +/- 79.41) ng/ml and (50.60 +/- 150.70) ng/ml respectively. Serum 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels of case and control were (7.43 +/- 11.10) ng/ml and (8.96 +/- 11.30) ng/ml respectively. No statistically significant differences were found between the two groups with geometric mean t-test (P > 0.05). Compared with women who had homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 homozygous variant genotype odds ratio (OR) = 2.61, 95% confidence interval (CI): 1.00 - 6.80]. Among premenopausal women, compared with women with homozygous wild-type of CYP1A1 genotype (Ile/Ile) and low serum DDT level (DDT serum level < or = 42.93 ng/ml), women with at least one variant allele of CYP1A1 m2 genotype and high serum DDT level (DDT serum level > or = 42.93 ng/ml) had higher risk of breast cancer (OR = 4.35, 95% CI: 1.140 - 16.950). CONCLUSIONS: CYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer while DDT exposure might have increased the risk of breast cancer among premenopausal women with CYP1A1 m2 variant genotype.