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Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma

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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.

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Acknowledgments

This study was supported by the Public Health Service grant R01CA-51932 from the National Cancer Institute, the National Center for Research Resources grant RR017698 from the National Institutes of Health, Department of Health and Human Services, the American Cancer Society Research Scholar grant RSG-06-122-01-CNE, and a Georgia Cancer Coalition Distinguished Scholar award (to R. Bostick), and National Cancer Institute, Center for Research and Cancer Health Disparities grant 1 U01 CA114601-01 (to JR Hebert).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA

    Zhihong Gong

  2. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Roberd M. Bostick

  3. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA

    Dawen Xie, Thomas G. Hurley, Zonglin Deng & James R. Hebert

  4. South Carolina Cancer Center, Columbia, SC, USA

    Dawen Xie, Thomas G. Hurley, Zonglin Deng, Dan A. Dixon & James R. Hebert

  5. South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA

    Thomas G. Hurley & James R. Hebert

  6. Department of Biological Sciences, University of South Carolina, Columbia, SC, USA

    Dan A. Dixon

  7. The Hormel Institute, University of Minnesota, Austin, MN, USA

    Jinhui Zhang

Authors
  1. Zhihong Gong
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  2. Roberd M. Bostick
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Correspondence to Dawen Xie.

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Gong, Z., Bostick, R.M., Xie, D. et al. Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma. Int J Colorectal Dis 24, 647–654 (2009). https://doi.org/10.1007/s00384-009-0656-8

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  • DOI: https://doi.org/10.1007/s00384-009-0656-8

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