Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: the Western New York Exposures and Breast Cancer (WEB) Study
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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.
KeywordsBreast cancer Cyclooxygenase-2 Non-steroidal anti-inflammatory drugs Prostaglandinendoperoxide synthase 2 Single nucleotide polymorphism
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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