MDM2启动子区309位点基因多态性与乳腺癌风险的关系

Association between MDM2 SNP309 Polymorphism and Breast Cancer Risk in Chinese Women

目的:采用病例-对照研究检测MDM2启动子区309位点T>G单核苷酸多态(SNP309)在中国女性人群中的频率分布,分析其与中国女性乳腺癌发病风险的关系。方法:提取病例组698例原发性乳腺癌患者及对照组525例健康人的外周血单核细胞DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法,检测MDM2启动子区309位点基因多态性,确定此位点三种基因型,即T/T、T/G、G/C基因型。统计分析病例组和对照组人群MDM2 SNP309各基因型频率分布,及各基因型与乳腺癌发病风险的相关性。结果:在研究的病例组与对照组整体人群中,经年龄、月经状态、家族史及生育史等因素校正后,与MDM2 SNP309 T/T基因型比较,T/G型及G/G型与乳腺癌的发病风险无显著相关性(T/G,adjusted OR=1.2,95%CI:O.8～1.6,P=0.30;G/G,adiusted OR=I.0,95%CI:0.7～1.5,P=0.88)。进一步分层分析后显示:在绝经后人群中,与T/T基因型比较,T/G基因型及G/G基因型显著增加乳腺癌的发病风险(T/G,adjusted OR=1.8,95%CI:1.2～3.0,P=0.011;G/G,adiusted OR=1.9,95%CI:1.2～33,P=0.014)。提示绝经后人群携带T/G型、G/G型者比携带T/T基因型者患乳腺癌的风险分别升高约1.8、1.9倍。在绝经前人群中,各基因型与乳腺癌的发病风险无显著相关性(P>0.05)。结论:MDM2启动子309位点突变型G等位基因携带者显著增加绝经后女性乳腺癌的发病风险。

Objective： To investigate the correlation of MDM2 SNP309 polymorphism with breast cancer risk in Chinese women. Methods： The polymorphism of MDM2 SNP309 was detected by PCR-restriction fragment length polymorphisms assay （PCR-RFLP） in 698 women with primary breast cancer and 525 healthy controls. Results： Compared with the T/T genotype, the G allele （T/G or G/G） was not associated with an increased risk of breast cancer in the entire population studied （T/G, adjusted OR=1.2, 95% CI： 0.8-1.6, P= 0.30; G/G, adjusted OR=1.0, 95% CI： 0.7 - 1.5, P=0.88）. Among postmenopausal women, the G allele （T/G or G/G） was significantly associated with an increased risk of breast cancer （T/G, adjusted OR=1.8, 95% CI： 1.2-3.0, P=0.011; G/G, adjusted OR=1.9, 95% CI： 1.2-3.3, P=0.014）. But this association was not observed among premenopausal women. Conclusion： MDM2 SNP309 heterozygous T/G genotype and homozygous mutant GIG genotype increase breast cancer risk in postmenopausal Chinese women.