Common variations in BARD1 influence susceptibility to high-risk neuroblastoma.
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.
Capasso
Mario
M
Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Devoto
Marcella
M
Hou
Cuiping
C
Asgharzadeh
Shahab
S
Glessner
Joseph T
JT
Attiyeh
Edward F
EF
Mosse
Yael P
YP
Kim
Cecilia
C
Diskin
Sharon J
SJ
Cole
Kristina A
KA
Bosse
Kristopher
K
Diamond
Maura
M
Laudenslager
Marci
M
Winter
Cynthia
C
Bradfield
Jonathan P
JP
Scott
Richard H
RH
Jagannathan
Jayanti
J
Garris
Maria
M
McConville
Carmel
C
London
Wendy B
WB
Seeger
Robert C
RC
Grant
Struan F A
SF
Li
Hongzhe
H
Rahman
Nazneen
N
Rappaport
Eric
E
Hakonarson
Hakon
H
Maris
John M
JM
D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D009447:Neuroblastoma / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases