title: COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancers in two independent populations.
abstract: OBJECTIVE
  Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and COX-2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy.
  
  
  METHODS
  We genotyped candidate polymorphisms and tag SNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case–control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n = 1,470 cases/1,837 controls) and rectal cancer (n = 583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n = 959/1,535, rectal n = 505/839).
  
  
  RESULTS
  In PTGS2, a functional polymorphism (-765G[C; rs20417) was associated with a twofold increased rectal cancer risk (p = 0.05) in the DALS. This association replicated with a significant nearly fivefold increased risk of rectal cancer in the CCFR study (ORCC vs. GG = 4.88; 95 % CI 1.54–15.45; ORGC vs. GG = 1.36; 95 %CI 0.95–1.94). Genotype–NSAID interactions were observed in the DALS for PTGS1 and rectal cancer risk and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed.
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Poole
authors.forename: Alexa J
authors.initials: AJ
authors.lastname: Resler
authors.forename: Brenna
authors.initials: B
authors.lastname: Seufert
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Kleinstein
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kulmacz
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.forename: John
authors.initials: J
authors.lastname: Whitton
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Christine F
authors.initials: CF
authors.lastname: Rimorin
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D051545:Cyclooxygenase 1 / Q000235:genetics* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D014861:Washington / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004273:DNA, Neoplasm; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human
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