Common variations in BARD1 influence susceptibility to high-risk neuroblastoma. Nat Genet

Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Nature Genetics (Impact Factor: 29.35). 06/2009; 41(6):718-23. DOI: 10.1038/ng.374
Source: PubMed


We conducted a SNP-based genome-wide association study (GWAS) focused on the high-risk subset of neuroblastoma. As our previous unbiased GWAS showed strong association of common 6p22 SNP alleles with aggressive neuroblastoma, we restricted our analysis here to 397 high-risk cases compared to 2,043 controls. We detected new significant association of six SNPs at 2q35 within the BARD1 locus (P(allelic) = 2.35 x 10(-9)-2.25 x 10(-8)). We confirmed each SNP association in a second series of 189 high-risk cases and 1,178 controls (P(allelic) = 7.90 x 10(-7)-2.77 x 10(-4)). We also tested the two most significant SNPs (rs6435862, rs3768716) in two additional independent high-risk neuroblastoma case series, yielding combined allelic odds ratios of 1.68 each (P = 8.65 x 10(-18) and 2.74 x 10(-16), respectively). We also found significant association with known BARD1 nonsynonymous SNPs. These data show that common variation in BARD1 contributes to the etiology of the aggressive and most clinically relevant subset of human neuroblastoma.

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Available from: Mario Capasso, Oct 06, 2015
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    • "Familial studies have identified genes that drive neuroblastoma, such as ALK (Janoueix-Lerosey et al., 2008; Mossé et al., 2008) and PHOX2B (Mosse et al., 2004; Trochet et al., 2004), in a subset of human cases. Conversely, high-powered genome-wide association studies (Capasso et al., 2009; Diskin et al., 2012; Nguyen et al., 2011; Wang et al., 2011) have succeeded in identifying numerous genes that confer a slightly increased risk for the disease . However, the complexity of the disease has confounded the search for druggable pathways. "
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    • "In particular, we found that several microRNAs could target the region around SNP rs7585356 (Fig. 2C). MiR- 513c and miR-514b-5p only target the neuroblastoma-associated " A " (Capasso et al., 2009) but not the " C " genotype of the SNP rs7585356. The rs7585356 genotype may also affect the targeting of microRNAs miR-588 and miR-668. "
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    • "The single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) were collected. These were associated with either breast cancer [31] [32], colorectal cancer [33] [34], endometrial cancer [35], follicular lymphoma [36], gastric cancer [37], hepatocellular carcinoma [38] [39], Hodgkin's lymphoma [40], lung cancer [41], melanoma [42], nasopharyngeal carcinoma [43], neuroblastoma [44], ovarian cancer [45] [46], pancreatic cancer [47] [48], prostate cancer [49] [50] [51] [52] [53] [54], renal cell carcinoma [55], thyroid cancer [56], or urinary bladder cancer [57]. We hypothesized that these genes, which are located within 100 kb of risk SNPs, are potentially cancer risk genes. "
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