Abstract
BRCA1-associated RING domain protein 1 (BARD1) is a tumor suppressor, which forms a heterodimer with BRCA1. Three BARD1 gene polymorphisms (rs7585356 G>A, rs6435862 T>G and rs3768716 A>G) were initially identified as high-risk neuroblastoma susceptibility loci by a previous GWAS. Because of the general tumor-suppressing function of BARD1, we hypothesized that these BARD1 gene polymorphisms might modify the susceptibility to nephroblastoma. We genotyped these polymorphisms in 145 cases and 531 controls using Taqman methods. Out of three polymorphisms, only the rs7585356 G>A polymorphism was significantly associated with increased susceptibility to nephroblastoma [AA vs. GG: adjusted odds ratio (OR)=1.78, 95% confidence interval (CI)=1.01-3.12]. Combined analysis of three polymorphisms indicated that subjects with 3 risk genotypes exhibited significantly elevated nephroblastoma risk, when compared with subjects with 0-2 risk genotypes (adjusted OR=1.72, 95% CI=1.02-2.89). Stratified analysis revealed that in term of clinical stage, rs7585356 AA carriers were associated with increased risk of developing clinical stage I+II nephroblastoma. The presence of three risk genotypes was significantly associated with nephroblastoma risk in females and clinical stage I+II nephroblastoma. Our results suggested that BARD1 rs7585356 G>A may be associated with nephroblastoma risk.