A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
;
Peter
Rudnai
;
Eugen
Gurzau
;
Kvetoslava
Koppova
;
Sophia CE
Bolick
;
Ashley
Godfrey
;
Zongli
Xu
;
José I
Sanz-Velez
;
María
D García-Prats
;
Manuel
Sanchez
;
Gabriel
Valdivia
;
Stefano
Porru
;
Simone
Benhamou
;
Robert N
Hoover
;
Joseph F
Fraumeni
;
Debra T
Silverman
;
Stephen J
Chanock
;
(2010)
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
Nature genetics, 42 (11).
pp. 978-984.
ISSN 1061-4036
DOI: 10.1038/ng.687
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
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