Common non-synonymous polymorphisms in the BRCA1 Associated RING Domain (BARD1) gene are associated with breast cancer susceptibility:a case-control analysis

查看全文 作　　者：Huo, [1]X;Hu, Z. [1]B;Zhai, X. [1]J;Wang, [1]Y;Wang, [1]S;Wang, X. [2]C;Qin, J. [1]W;Chen, W. [1]S;Jin, G. [3]F;Liu, J. [4]Y;Gao, [1]J;Wei, Q. [5]Y;Wang, X. [4]R;Shen, H. [1]B 机构地区：[1]Nanjing Med Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Nanjing 210029, Peoples R China;[2]Nanjing Med Univ, Lab Reprod Med, Nanjing 210029, Peoples R China;[3]Nanjing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Nanjing 210029, Peoples R China;[4]Nanjing Gulou Hosp, Dept Gen Surg, Nanjing, Peoples R China;[5]Jiangsu Canc Hosp, Dept Gen Surg, Nanjing 210009, Peoples R China 出　　处：《南京医科大学学报(自然科学版)》索引2007年第27卷第7期,共1页 摘　　要：The BRCA1 Associated RING Domain(BARD1) gene has been identified as a high penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer cases. BARD1 plays a crucial role in tumor repression, along with its heterodimeric partner BRCA1. In the current study, we tested the hypothesis that common non-synonymous polymorphisms in BARD1 are associated with breast cancer susceptibility in a case-control study of 507 patients with incident breast cancer and 539 frequency-matched cancer-free controls in Chinese women. We genotyped all three common(minor allele frequency (MAF) > 0.10) non-synonymous polymorphisms(Pro24Ser, Arg378Ser, and Val507Met) in BARD1. We found that the BARD1 Pro24Ser variant genotypes(24Pro/Ser and 24Ser/Ser) and Arg378Ser variant homozygote 378Ser/Ser were associated with a significantly decreased breast cancer risk, compared with their wild-type homozygotes, respectively. Furthermore, a significant locus-locus interaction was evident between Pro24Ser and Arg378Ser (P-int = 0.032). Among the 378Ser variant allele carriers, the 24Pro/Pro wild-type homozygote was associated with a significantly increased breast cancer risk (adjusted OR = 1.81, 95% CI = 1.11-2.95), but the subjects having 24Pro/Ser or Ser/Ser variant genotypes had a significantly decreased risk(adjusted OR = 0.74, 95% CI = 0.56-0.99). In stratified analysis, this locus-locus interaction was more evident among subjects without family cancer history, those with positive estrogen receptor (ER) and individuals with negative progesterone receptor(PR). These findings indicate that the potentially functional polymorphisms Pro24Ser and Arg378Ser in BARD1 may jointly contribute to the susceptibility of breast cancer. 关 键 词：乳腺癌 环形域基因 基因多态性 BRCA1 基因突变