Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women
Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women
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DOI：
10.1007/s00432-009-0604-6
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发表时间：
2009-11-01
影响因子：
3.6
通讯作者：
Tang, Jinhai
中科院分区：
文献类型：
--
作者：
Huo, Xiang;Lu, Cheng;Tang, Jinhai
BRCA1 相互作用蛋白 C 末端解旋酶 1 (BRIP1) 和锌指蛋白 350 (ZNF350) 在肿瘤抑制过程中与 BRCA1 协同作用。这三个基因的低外显率变异可能共同影响普通人群中个体的乳腺癌易感性。我们重点关注BRIP1、ZNF350和BRCA1编码区中潜在的功能性单核苷酸多态性(SNP)，并采用成对标记方法来最大限度地减少SNP的数量。在一项针对中国人群的 568 例乳腺癌病例和 624 名对照的病例对照研究中，选择了 5 个 SNP，并通过 PCR 限制性片段长度多态性或 PCR 引物引入限制性分析测定进行了基因分型。除了 ZNF350 的 rs2278415 之外，所有 5 个 SNP 均导致风险适度增加，但没有统计学意义。联合效应分析表明，ZNF350 多态性的所有变异基因型均导致携带 BRCA1 rs799917 变异纯合子的受试者患乳腺癌的风险增加，特别是 ZNF350 rs4986773（OR = 2.03，95%CI = 1.02-4.05，基因-基因相互作用检验 P (int) = 0.059）。 ZNF350可能共同导致中国女性个体对乳腺癌的易感性。有必要进行进一步的功能研究来验证我们的发现。
BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population.We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population.All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059).BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings.