title: Use of analgesics and nonsteroidal anti-inflammatory drugs, genetic predisposition, and bladder cancer risk in Spain.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Research in Environmental Epidemiology, Municipal Institute of Medical Research, Autonomous University of Barcelona [corrected] Barcelona, Catalonia, Spain. jfortuny@imim.es
authors.forename: Joan
authors.initials: J
authors.lastname: Fortuny
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.forename: Reina
authors.initials: R
authors.lastname: Garcia-Closas
authors.forename: Consol
authors.initials: C
authors.lastname: Serra
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.forename: Nat
authors.initials: N
authors.lastname: Rothman
authors.forename: Cristina
authors.initials: C
authors.lastname: Villanueva
authors.forename: Mustafa
authors.initials: M
authors.lastname: Dosemeci
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.forename: Debra
authors.initials: D
authors.lastname: Silverman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000235:genetics
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi