【摘要】 目的:探讨肿瘤抑制基因BARD1的单核苷酸多态性与乳腺癌易感性的关系。方法:运用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)分析的方法检测422例中国汉族女性乳腺癌患者和476名正常女性对照者BARD1基因Pro24Ser(rs1048108)和Arg378Ser(rs2229571)位点的基因型,以SAS9.1.3软件进行数据处理。结果:Pro24Ser(rs1048108)和Arg378Ser(rs2229571)多态性位点的基因型分布在病例对照组间存在显著差异。与野生型(24CC,378GG)相比,Pro24Ser位点突变基因型(CT/TT)和Arg378Ser位点的杂合型(GC)均能够显著降低乳腺癌的发病风险(调整OR和95%CI分别为0.64,0.49～0.84;0.54,0.3～0.86)。并且位点间还存在协同作用,携带一个以上保护等位基因者与携带0-1个者相比,乳腺癌的发病风险显著降低(调整OR=0.67,95%CI=0.51～0.87)。分层分析表明,Pro24Ser位点的保护作用在52岁以下年龄组、绝经前妇女、无肿瘤家族史者和Arg378Ser位点发生突变者中更强。结论:BARD1基因Pro24Ser(rs1048108)和Arg378Ser(rs2229571)单核苷酸多态性改变能够显著降低中国人群乳腺癌的发病风险,这一结论有待进一步大样本、不同种族人群的关联研究以及功能学研究的证实。更多还原

【Abstract】 Objective:To investigate the association between two polymorphisms of BARD1 gene and the susceptibility of breast cancer in a Chinese population. Methods:Genotyping were performed using PCR-restriction fragment length polymorphism(PCR-RFLP) assay in 422 histological-confirmed breast cancer cases and 476 age frequency-matched cancer-free controls. Results:The genotypes distribution of the BARD1 Pro24Ser(rs1048108) and Arg378Ser(rs2229571) polymorphisms were significantly different between cases and controls. Multivariate logistic regression analysis revealed that variant genotypes of Pro24Se polymorphism(CT/TT) and heterozygotes of Arg378Ser polymorphism were both associated with a significantly decreased risk of breast cancer(adjusted OR=0.64,95%CI=0.49-0.84;adjusted OR=0.54,95%CI= 0.33-0.86,respectively) compared with the wild-type genotype(24CC and 378GG). Furthermore,these two polymorphisms may have joint effect on breast cancer risk. Individuals with more than one protective allele showed a significantly decreased risk compared with those with 0-1 protective allele(adjusted OR=0.67,95% CI=0.51-0.87). Stratified analysis showed that the protective effect of Pro24Ser polymorphism was more evident in subjects with age less than 52,premenopausal status,without family history of cancer and Arg378Ser variant genotypes carriers. Conclusion:Pro24Ser(rs1048108)and Arg378Ser(rs2229571) polymorphisms of BARD1gene were associated with a significantly decreased risk of breast cancer. And these two polymorphisms may jointly affect individuals’ susceptibility. More rigorous laboratory studies and larger epidemiological studies with ethnically diverse populations are warranted to confirm our findings.更多还原