Journal
CANCER RESEARCH
Volume 69, Issue 17, Pages 6857-6864Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-1091
Keywords
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Categories
Funding
- Ligue contre le Cancer du Val-de-Marne
- Fondation de France
- Groupement d'Entreprises Francaises dans la Lutte contre le Cancer
- Association pour la Recherche stir le Cancer, France
- National Cancer Institute [R01 CA74880, 1P01CA86871, 1R01CA114665, N02-CP-11015]
- Cancer Research UK
- Yorkshire Cancer Research
- NIH [K07 CA102327, R03 CA121382, R01CA57494, P42 ES007373, ES06718, CA09142]
- Italian Association for Cancer Research
- Ministry of Health, Oncology Integrated Project
- University of California at Los Angeles Johnsson Comprehensive Cancer Center
- Cancer Research UK [10589] Funding Source: researchfish
- NATIONAL CANCER INSTITUTE [R01CA057494, K07CA102327, R01CA114665, R03CA121382, P01CA086871, R01CA074880, ZIACP010121, R01CA111922, T32CA009142] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES006718, ZIAES049033, P42ES007373] Funding Source: NIH RePORTER
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Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01-1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01-1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% Cl, 1.00-1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. [Cancer Res 2009;69(17):6857-64]
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