Functional Polymorphisms in BARD1 Association with Neuroblastoma in a regional Han Chinese Population

Neuroblastoma (NB) is a sympathetic nervous system cancer for children, occupying approximately 15% of pediatric oncology deaths. BARD1, a tumor suppressor, is essential for genome stability by interaction with BRCA1. Here, we performed a systematic investigation for the association between SNPs in BARD1 and the risk of NB in Chinese population. After SNP screening in BARD1 gene, we performed case-control study of eleven selected SNPs in BARD1 with 339 NB patients and 778 cancer-free controls. The OR and 95% CI of these candidate SNPs were computed by logistic regression. After adjusted gender and age, seven out of eleven SNPs in BARD1 were significant associated with the risk of NB, including one SNP in 5'-UTR (rs17489363 G > A), two SNPs in exon (rs2229571 G > C and rs3738888 C > T), and four SNPs in intron (rs3768716 A > G, rs6435862 T > G, rs3768707 C > T and rs17487792 C > T). When stratified by the INPC, primary tumor site and the INSS, these seven SNPs were significant associated with GNB/NB, stage III/IV and adrenal origin of NB. Dual-luciferase reporter assay showed rs17489363 A allele-containing haplotypes (TAC, CAC, TAG and CAG), composed with rs34732883 T > C, and rs1129804 C > G, dramatically reduced the transcriptional activity of reporter gene. The major of our study showed that seven SNPs of BARD1 associated with increased NB risk in Chinese population, and four haplotypes could reduce transcription activity of BARD1.