Epidemiology

Breast Cancer Research and Treatment

, Volume 126, Issue 1, pp 157-165

Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: the Western New York Exposures and Breast Cancer (WEB) Study

  • Theodore M. BraskyAffiliated withDepartment of Social and Preventive Medicine, School of Public Health and Health Professions, University at BuffaloFred Hutchinson Cancer Research Center Email author 
  • , Matthew R. BonnerAffiliated withDepartment of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo
  • , Kirsten B. MoysichAffiliated withDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute
  • , Heather M. Ochs-BalcomAffiliated withDepartment of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo
  • , Catalin MarianAffiliated withLombardi Comprehensive Cancer Center, Georgetown University
  • , Christine B. AmbrosoneAffiliated withDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute
  • , Jing NieAffiliated withDepartment of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo
  • , Meng Hua TaoAffiliated withDepartment of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo
  • , Stephen B. EdgeAffiliated withDepartment of Surgery, Roswell Park Cancer Institute
    • , Maurizio TrevisanAffiliated withNevada System of Higher Education
    • , Peter G. ShieldsAffiliated withLombardi Comprehensive Cancer Center, Georgetown University
    • , Jo L. FreudenheimAffiliated withDepartment of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo

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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.

Keywords

Breast cancer Cyclooxygenase-2 Non-steroidal anti-inflammatory drugs Prostaglandinendoperoxide synthase 2 Single nucleotide polymorphism