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Title: [Association between single nucleotide polymorphisms of BARD 1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang].
Author: Sun G, Wang JT, Ma BL, Geng ZL, Ren GH, Shan MH, Ma B, Ma LL, Wang Y.
Journal: Zhonghua Zhong Liu Za Zhi; 2012 May; 34(5):341-7. PubMed ID: 22883453.
Abstract:
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-restriction fragment length polymorphism (PCR-RFLP) assay, in 144 early-onset breast cancer cases of Uygur women (≤ 40 years) and 136 cancer-free controls matched by age and ethnicity. The association between SNPs of BARD1 gene and risk of early-onset 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 Uygur 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 Uygur 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 dominance-genotypes (CT+TT, GC+CC and GA+AA) showed a 52.1% lower incidence of early-onset breast cancer in Uygur women (OR = 0.479, 95%CI = 0.230 - 0.995). Stratified analysis indicated that the protective effect of carrying T variant genotype (CT/TT) 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 menarche 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.

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