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

  • Epidemiology
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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.

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Acknowledgments

This work was supported in part by grants DAMD-17-03-1-0446 and DAMD-17-96-1-6202 from the U.S. Department of Defense Breast Cancer Research Program, and NCI RO1CA92040, NIAAA P50-AA09802, K05CA154337, and R25-CA94880 from the National Institutes of Health. Dr. Ambrosone is a recipient of funding from the Breast Cancer Research Foundation.

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Authors and Affiliations

  1. Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA

    Theodore M. Brasky, Matthew R. Bonner, Heather M. Ochs-Balcom, Jing Nie, Meng Hua Tao & Jo L. Freudenheim

  2. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA

    Kirsten B. Moysich & Christine B. Ambrosone

  3. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

    Catalin Marian & Peter G. Shields

  4. Department of Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA

    Stephen B. Edge

  5. Nevada System of Higher Education, Las Vegas, NV, USA

    Maurizio Trevisan

  6. Fred Hutchinson Cancer Research Center, M4-B402, 1100 Fairview Ave. N., Seattle, WA, 98109-1024, USA

    Theodore M. Brasky

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  1. Theodore M. Brasky
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Correspondence to Theodore M. Brasky.

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Brasky, T.M., Bonner, M.R., Moysich, K.B. et al. 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 Res Treat 126, 157–165 (2011). https://doi.org/10.1007/s10549-010-1082-x

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