학술논문
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
Document Type
Article
Author
Rothman, Nathaniel; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Malats, Nuria; Xifeng Wu; Figueroa, Jonine D.; Real, Francisco X.; Van Den Berg, David; Matullo, Giuseppe; Baris, Dalsu; Thun, Michael; Kiemeney, Lambertus A.; Vineis, Paolo; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P.; Rafnar, Thorunn; Hildebrandt, Michelle A. T.; Kiltie, Anne E.; Cussenot, Olivier
Source
Subject
*BLADDER cancer
*DISEASE susceptibility
*LOCUS (Genetics)
*GENOMES
*CARCINOGENESIS
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Language
ISSN
1061-4036
Abstract
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. [ABSTRACT FROM AUTHOR]