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Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma
Authors:Zhihong Gong  Roberd M. Bostick  Dawen Xie  Thomas G. Hurley  Zonglin Deng  Dan A. Dixon  Jinhui Zhang  James R. Hebert
Affiliation:1. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
2. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
3. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
4. South Carolina Cancer Center, Columbia, SC, USA
5. South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA
6. Department of Biological Sciences, University of South Carolina, Columbia, SC, USA
7. The Hormel Institute, University of Minnesota, Austin, MN, USA
Abstract:Purpose  Cyclooxygenase (COX) enzymes, COX1 and COX2, are key in converting arachidonic acid (AA) into prostaglandins that have been associated with colorectal carcinogenesis. The aim of our study was to investigate associations of polymorphisms in COX genes, alone and in interaction with exposures known to be related to inflammation and AA metabolism, with risk of colorectal adenomas. Materials and methods  In a community-, colonoscopy-based case–control study with 162 incident, sporadic colorectal adenoma cases and 211 controls, we investigated associations of two promoter polymorphisms (−842 A  > G in COX1 and −765 G > C in COX2) and two polymorphisms in the 3′-UTR of COX2 (8473 T > C and 9850 A > G) with risk of adenomas. Multiple logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of colorectal adenoma after adjusting for potential confounders. Results  Overall, there was no evidence for an association between any of the four polymorphisms and colorectal adenomas. However, we found a statistically significant interaction between the COX2 8473 T > C polymorphism and nonsteroidal anti-inflammatory drug (NSAIDs) use (P interaction = 0.03): The greatest reduced risk was observed for individuals with the 8473 C variant allele who also regularly used NSAIDs (OR = 0.35, 95% CI 0.16–0.75). Conclusion  These results suggest that the C allele of COX2 8473 T > C polymorphism may interact with NSAIDs to reduce risk for colorectal adenoma.
Keywords:COX1  COX2  Polymorphisms  Inflammation  Colorectal adenoma
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