title: Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: the Western New York Exposures and Breast Cancer (WEB) Study.
abstract: Chronic inflammation has been consistently associated with cancers of several sites, including the breast, and inhibition of inflammation through the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been inversely associated with risk. As NSAIDs bind with cyclooxygenase-2 (COX-2), genetic variation in COX-2 may influence breast cancer risk by affecting inflammatory response and response to NSAID use. We identified eight single nucleotide polymorphisms (SNPs) for COX-2 and examined their association with risk of breast cancer in a population-based case-control study in Western New York. Cases had incident, first primary, histologically confirmed breast cancer (n = 1077). Controls (n = 1910) were randomly selected from NY Department of Motor Vehicles records (< 65) or Medicare rolls (≥ 65). Participants were queried on adult lifetime use of aspirin and recent use of ibuprofen. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). One SNP, rs2745559, was associated with an increased risk of breast cancer (OR 1.23, 95% CI 1.03-1.46). Associations with other variants were not evident. Significant interaction (P interaction = 0.04) between recent aspirin use and rs4648261 was also observed. Variation in COX-2 was modestly associated with breast cancer risk, indicating that COX-2 may play a role in breast carcinogenesis. Better understanding of the role of COX-2 genetic variation and interaction with NSAID use in breast carcinogenesis has potential to inform prevention strategies.
authors.affiliation: Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA. tbrasky@fhcrc.org
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Brasky
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Bonner
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Moysich
authors.forename: Heather M
authors.initials: HM
authors.lastname: Ochs-Balcom
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Meng Hua
authors.initials: MH
authors.lastname: Tao
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Edge
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trevisan
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D017322:Clinical Trials, Phase II as Topic; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004273:DNA, Neoplasm; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001241:Aspirin; D007052:Ibuprofen