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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.

Original publication

DOI

10.1038/ng.687

Type

Journal article

Journal

Nature genetics

Publication Date

11/2010

Volume

42

Pages

978 - 984

Addresses

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Keywords

Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 18, Chromosomes, Human, Pair 22, Humans, Genetic Predisposition to Disease, Arylamine N-Acetyltransferase, Neoplasm Staging, Incidence, Risk Assessment, Risk Factors, Chromosome Mapping, Smoking, Family, Sex Characteristics, Polymorphism, Single Nucleotide, United States, Europe, Spain, Female, Male, Urinary Bladder Neoplasms, Genome-Wide Association Study