title: Nonsteroidal anti-inflammatory drugs and other analgesic use and bladder cancer in northern New England.
abstract: A few epidemiologic studies have found that use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with reduced risk of bladder cancer. However, the effects of specific NSAID use and individual variability in risk have not been well studied. We examined the association between NSAIDs use and bladder cancer risk, and its modification by 39 candidate genes related to NSAID metabolism. A population-based case-control study was conducted in northern New England, enrolling 1,171 newly diagnosed cases and 1,418 controls. Regular use of nonaspirin, nonselective NSAIDs was associated with reduced bladder cancer risk, with a statistically significant inverse trend in risk with duration of use (ORs of 1.0, 0.8, 0.6 and 0.6 for <5, 5-9, 10-19 and 20+ years, respectively; p(trend)  = 0.015). This association was driven mainly by ibuprofen; significant inverse trends in risk with increasing duration and dose of ibuprofen were observed (p(trend)  = 0.009 and 0.054, respectively). The reduced risk from ibuprofen use was limited to individuals carrying the T allele of a single nucleotide polymorphism (rs4646450) compared to those who did not use ibuprofen and did not carry the T allele in the CYP3A locus, providing new evidence that this association might be modified by polymorphisms in genes that metabolize ibuprofen. Significant positive trends in risk with increasing duration and cumulative dose of selective cyclooxygenase (COX-2) inhibitors were observed. Our results are consistent with those from previous studies linking use of NSAIDs, particularly ibuprofen, with reduced risk. We observed a previously unrecognized risk associated with use of COX-2 inhibitors, which merits further evaluation.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, North Bethesda, MD 20852, USA. barisd@mail.nih.gov
authors.forename: Dalsu
authors.initials: D
authors.lastname: Baris
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: Stella
authors.initials: S
authors.lastname: Koutros
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Colt
authors.forename: Alison
authors.initials: A
authors.lastname: Johnson
authors.forename: Molly
authors.initials: M
authors.lastname: Schwenn
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Fischer
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Summer
authors.initials: S
authors.lastname: Han
authors.forename: Laura E
authors.initials: LE
authors.lastname: Beane Freeman
authors.forename: Jay H
authors.initials: JH
authors.lastname: Lubin
authors.forename: Sai
authors.initials: S
authors.lastname: Cherala
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Cantor
authors.forename: Kevin
authors.initials: K
authors.lastname: Jacobs
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D016022:Case-Control Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D008875:Middle Aged; D009511:New England / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007052:Ibuprofen