A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

Journal article

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.

Authors: Rothman, N; Garcia-Closas, M; Chatterjee, N; Malats, N; Wu, X

• Publication status: Published
• Journal: Nature genetics
• Volume: 42
• Issue: 11
• Pages: 978-984
• Publication date: 2010-11-01
• DOI: 10.1038/ng.687
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Risk Factors; Risk Assessment; Chromosomes, Human, Pair 22; Incidence; Spain; Sex Characteristics; Chromosomes, Human, Pair 2; Polymorphism, Single Nucleotide; Arylamine N-Acetyltransferase; Europe; Chromosomes, Human, Pair 18; Female; Urinary Bladder Neoplasms; Chromosome Mapping; Smoking; Genetic Predisposition to Disease; Humans; United States; Genome-Wide Association Study; Family; Male; Neoplasm Staging