BARD1基因单核苷酸多态性与新疆维吾尔族妇女早发性乳腺癌的相关性研究

Association between single nucleotide polymorphisms of BARD1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang

目的探讨BARD1基因Pr024Ser（C／T）、Arg378Ser（G／C）和Val507Met（G／A）单核苷酸多态性（SNPs）与新疆维吾尔族妇女早发性乳腺癌易感性的关系。方法采用病例一对照研究，应用聚合酶链反应．限制性片段长度多态性（PCR—RFLP）方法检测新疆地区144例维吾尔族妇女早发性乳腺癌（年龄≤40岁）和136例维吾尔族健康女性BARDl基因Pr024Ser（C／T）、Arg378Ser（G／C）和Val507Met（G／A）位点基因型，比较各位点基因型分布与维吾尔族妇女早发性乳腺癌发病风险的关系。结果初潮年龄早、初产年龄晚和肿瘤家族史可能是新疆地区维吾尔族早发性乳腺癌患者发病的高危因素。在维吾尔族早发性乳腺癌组和健康对照组中，BARDl基因Pr024Ser（C／T）、Arg378Ser（G／C）和Val507Met（G／A）位点的各基因型频率差异有统计学意义（P〈0．05）。Logistic回归分析表明，Pr024Ser（C／T）位点Tr（OR=0．117，95％CI为0．058—0．236）及显性模型CT＋TT（OR=0．279，95％口为0．157—0．494）、Arg378Ser（G／C）位点CC（OR=0．348，95％CI为0．145～0．834）和Val507Met（G／A）位点AA（OR=0．359，95％CI为0．167—0．774）的改变，可以显著降低维吾尔族早发性乳腺癌发病风险，并且各位点之间存在协同作用；同时，显性模型CT＋TF、GC＋CC、GA＋AA间的交互作用可以降低52．1％的乳腺癌发病风险（OR=0．479，95％CI为0．230—0．995）。分层分析结果显示，Pr024Ser（C／T）和Arg378Ser（G／C）位点基因突变型的保护作用在初潮年龄早和肿瘤家族史阴性患者中更为明显。随着患者初潮年龄的增加，这种保护作用逐渐降低。结论BARDl基因Pr024Ser（C／T）、Arg378Ser（G／C）和Val507Met（G／A）位点的SNPs变化，能够显著降低新疆地区维吾尔族妇女早发性乳腺癌的发病风险，初潮年龄早和无肿瘤家族史可以增加突变等位基因的保护作用。

Objective To investigate the association between single nucleotide polymorphisms （SNPs） of BARD1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang. Methods A case-control study was designed to explore the genotypes of Pro24Ser （C/T） , Arg378Ser （G/ C） and Val507Met （G/A） of BARD1 gene, detected by PCR-restrlction fragment length polymorphism （PCR-RFLP） assay, in 144 early-onset breast cancer cases of Uygur women （ ≤40 years） and 136 cancerfree controls matched by age and ethnicity. The association between SNPs of BARD1 gene and risk of earlyonset breast cancer in Uygur women was analyzed by unconditional logistic regression model. Results Early age at menarche, late age at first pregnancy, and positive family history of cancer may be important risk factors of early-onset breast cancer in Uygnr women in Xinjiang. The frequencies of genotypes of Pro24Ser （ C/T）, Arg378Ser （G/C） and Val507Met （G/A） of BARD1 gene showed significant differences between the cancer cases and cancer-free controls （ P 〈 0.05 ）. Compared with wild-type genotype Pro24Ser CC, it showed a lower incidence of early-onset breast cancer in Uygnr women with variant genotypes of Pro24Ser TT （ OR =0. 117,95% CI= 0. 058-0. 236）, and dominance-genotype CT ＋TT （OR =0.279,95% CI=0. 157- 0.494）, or Arg378Ser CC （OR =0. 348,95% CI =0. 145-0. 834） and Val507Met AA（OR =0. 359, 95% CI =0. 167-0. 774）. Furthermore, SNPS in three polymorphisms would have synergistic effects on the risk of breast cancer. In addition,the SNP-SNP interactions of dominanee-genotypes（ CT ＋ TT, GC ＋ CC and GA ＋ AA） showed a 52.1% lower incidence of early-onset breast eancer in Uygur women （ OR = 0. 479, 95% CI = 0.230-0. 995 ）. Stratified analysis indicated that the proteetive effect of carrying T variant genotype （CT/TF） in Pro24Ser and carrying C variant genotype （GC/CC） in Arg378Ser were more evident in subjects with early age at menarche and negative family history of cancer. With an older menarehe age, the protective effect was weaker. Conclusions SNPs of Pro24Ser （C/T）, Arg378Ser （G/C） and Val507Met （G/A） of BARD1 gene are associated with significantly decreased risk of early-onset breast cancer in Uygur women in Xinjiang. Early age at menarche and negative family history of cancer can enhance the protective effect of mutant allele.