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Use of Analgesics and Nonsteroidal Anti-inflammatory Drugs, Genetic Predisposition, and Bladder Cancer Risk in Spain

¹ Centre for Research in Environmental Epidemiology, Institut Municipal d'Investigació Mèdica, Barcelona, Catalonia, Spain; ² Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica; ³ Universitat Pompeu Fabra, Barcelona, Catalonia, Spain; ⁴ Department of Pathology, Hospital del Mar-IMAS-Institut Municipal d'Investigació Mèdica, Barcelona, Catalonia, Spain; ⁵ Medical School of Crete, Greece; ⁶ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland; ⁷ Universidad de Oviedo, Oviedo, Spain; ⁸ Hospital Universitario de Canarias, La Laguna, Spain; ⁹ Consorci Hospitalari Parc Taulí, Sabadell, Catalonia, Spain; and ¹⁰ Hospital General Universitari d'Elx, Elx, Spain

Requests for reprints: Joan Fortuny, Centre for Research in Environmental Epidemiology, Municipal Institute of Medical Research, Barcelona, Catalonia, Spain. E-mail: jfortuny{at}imim.es

Background: We assessed use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAID), aspirin, paracetamol (acetaminophen), phenacetin, and metamizol (dipyrone) and risk of bladder cancer and their interaction with polymorphisms in drug-metabolizing genes.

Methods: We analyzed personal interview data from 958 incident bladder cancer cases and 1,029 hospital controls from a multicenter case-control study in Spain. A drug matrix was developed to estimate cumulative lifetime dose of active ingredients. Polymorphisms in GSTP1, SULT1A1, CYP2E1, CYP2C9, and NAT2 were examined.

Results: A significant reduction in bladder cancer risk [adjusted odds ratio (OR), 0.4; 95% confidence interval (95% CI), 0.2-0.9] was observed for regular users of nonaspirin NSAIDs compared with never users. Regular users of aspirin experienced no reduction in risk (OR, 1.0; 95% CI, 0.7-1.5). Regular users of paracetamol had no overall increased risk of bladder cancer (OR, 0.8; 95% CI, 0.4-1.3), but our data suggested a qualitative interaction with the GSTP1 I105V genotype. Subjects with at least one copy of the 359L or 144C variant alleles in the NSAID-metabolizing gene CYP2C9 had a slightly decreased risk of bladder cancer (OR, 0.8; 95% CI, 0.7-1.0; P = 0.037); however, having at least one copy of the 359L or 144C variant alleles did not significantly modify the protective effect of nonaspirin NSAID use.

Conclusion: Regular use of nonaspirin NSAIDs was associated with a reduced risk of bladder cancer, which was not modified by polymorphisms in the NSAID-metabolizing gene CYP2C9. We found no evidence of an overall effect for paracetamol or aspirin use. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1696–703)

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				C. M. Villanueva, D. T. Silverman, N. Malats, A. Tardon, R. Garcia-Closas, C. Serra, A. Carrato, J. Fortuny, N. Rothman, M. Dosemeci, et al. Determinants of Quality of Interview and Impact on Risk Estimates in a Case-Control Study of Bladder Cancer Am. J. Epidemiol., May 28, 2009; (2009) kwp136v1. [Abstract] [Full Text] [PDF]