Relationship Between Single Nucleotide Polymorphisms Of BARD1Gene And Susceptibility Of Early-onset Breast Cancer Of Uygur Women In Xinjiang

Objective To investigate the relationship between single nucleotide polymorphisms(SNPs) of BARD1gene and susceptibility of early-onset breast cancer of Uygur womenin Xinjiang. Methods A case-control study was designed to describe the genotypes ofPro24Ser (C/T),Arg378Ser (G/C) and Val507Met (G/A) of BARD1gene,which weredetected by PCR-restriction fragment length polymorphism (PCR-RFLP) assay in144early-onset breast cancer cases of Uygur women (≤40years) and136cancer-freecontrols,who were matched by age and ethnic. The relationship between SNPs of BARD1gene and risk of early-onset breast cancer of Uygur women was analyzed by unconditionallogistic regression model. Results (1) Early age at menarche,late age at firstpregnancy,and positive family history of cancer may be important risk factors ofearly-onset breast cancer of Uygur women in Xinjiang.(2) The frequencies of genotypesof Pro24Ser (C/T)、Arg378Ser (G/C) and Val507Met (G/A) of BARD1gene showedsignificant differences between cases and cancer-free controls (P<0.05).(3) Comparedwith wild-type genotype Pro24Ser CC,it showed a lower incidence of early-onset breastcancer of 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 Dominance-Genotype GC+CC (OR=0.650,95%CI=0.403~1.048). Compared with wild-type genotypeGG,Variant genotypes of Val507Met GA+AA (OR=0.759,95%CI=0.473~1.219) wereassociated with a less significant decreased risk of breast cancer. Furthermore,SNPS inthree polymorphisms would have combined effects on the risk of breast cancer. Inaddition,the SNP-SNP interactions of dominance-Genotypes（CT+TT、GC+CC andGA+AA）showed a52.0%lower incidence of early-onset breast cancer of Uygur womenon (OR=0.479,95%CI=0.230~0.995).(4) Stratified analysis indicated that the protective effects of carrying T variant genotype (CT/TT) in Pro24Ser and carrying C variantgenotype (GC/CC) in Arg378Ser were more evident in subjects with early age atmenarche and negative family history of cancer. With the menarche age was older,theprotective effect was weaker. Conclusions SNPs of Pro24Ser(C/T),Arg378Ser (G/C) andVal507Met (G/A) of BARD1gene were associated with significant decreased risks ofearly-onset breast cancer of Uygur women in Xinjiang. Early age at menarche andnegative family history of cancer can increase the protective effects of mutant allele.