Letter abstract
Nature Genetics 41, 718 - 723 (2009)
Published online: 3 May 2009 | doi:10.1038/ng.374
Common variations in BARD1 influence susceptibility to high-risk neuroblastoma
Mario Capasso1,2,3, Marcella Devoto1,2,4,5, Cuiping Hou6, Shahab Asgharzadeh7, Joseph T Glessner6, Edward F Attiyeh2,8, Yael P Mosse2,8, Cecilia Kim6, Sharon J Diskin2,8, Kristina A Cole2,8, Kristopher Bosse2,8, Maura Diamond2,8, Marci Laudenslager2,8, Cynthia Winter2,8, Jonathan P Bradfield6, Richard H Scott9, Jayanti Jagannathan8, Maria Garris6, Carmel McConville10, Wendy B London11, Robert C Seeger7, Struan F A Grant1,2,6, Hongzhe Li4, Nazneen Rahman9, Eric Rappaport2,8, Hakon Hakonarson1,2,6 & John M Maris2,8,12
We conducted a SNP-based genome-wide association study (GWAS) focused on the high-risk subset of neuroblastoma1. As our previous unbiased GWAS showed strong association of common 6p22 SNP alleles with aggressive neuroblastoma2, 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 (Pallelic = 2.35 
10-9–2.25 10-8). We confirmed each SNP association in a second series of 189 high-risk cases and 1,178 controls (Pallelic = 7.90 10-7–2.77 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 10-18 and 2.74 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.
- Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
- Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
- University "Federico II", CEINGE - Biotecnologie Avanzate, Naples, Italy.
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
- University of Rome "La Sapienza", Department of Experimental Medicine, Rome, Italy.
- The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
- Division of Hematology – Oncology and Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
- Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
- Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
- School of Cancer Sciences, University of Birmingham, UK.
- Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, Florida, USA.
- Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Correspondence to: Marcella Devoto1,2,4,5 e-mail: devoto@chop.edu
Correspondence to: Hakon Hakonarson1,2,6 e-mail: hakonarson@chop.edu
Correspondence to: John M Maris2,8,12 e-mail: maris@chop.edu
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