[Association between single nucleotide polymorphisms of BARD 1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang].

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.