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. Brasky, Matthew R. Bonner, Kirsten B. Moysich, Heather M. Ochs-Balcom, Catalin Marian, Christine B. Ambrosone, Jing Nie, Meng Hua Tao, Stephen B. Edge, Maurizio Trevisan, Peter G. Shields, Jo L. Freudenheim

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)157-165
Number of pages9
JournalBreast Cancer Research and Treatment
Volume126
Issue number1
DOIs
StatePublished - Feb 2011

Keywords

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

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    Brasky, T. M., Bonner, M. R., Moysich, K. B., Ochs-Balcom, H. M., Marian, C., Ambrosone, C. B., Nie, J., Tao, M. H., Edge, S. B., Trevisan, M., Shields, P. G., & Freudenheim, J. L. (2011). Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: The Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Research and Treatment, 126(1), 157-165. https://doi.org/10.1007/s10549-010-1082-x