title: Common non-synonymous polymorphisms in the BRCA1 Associated RING Domain (BARD1) gene are associated with breast cancer susceptibility: a case-control analysis.
abstract: 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.
authors.affiliation: Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Huo
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhai
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
authors.forename: Xuechen
authors.initials: X
authors.lastname: Wang
authors.forename: Jianwei
authors.initials: J
authors.lastname: Qin
authors.forename: Wenseng
authors.initials: W
authors.lastname: Chen
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D044466:Asian People; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D008969:Molecular Sequence Data; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases