Research article
Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk
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* Corresponding author: Jing Shen js2182@columbia.edu
1 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 630 West 168th Street, New York, New York 10032, USA
2 Department of Epidemiology, School of Public Health, University of North Carolina, CB#7435 McGavern-Greenberg Hall, Chapel Hill, North Carolina 27599, USA
3 Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, New York 10032, USA
4 Department of Community and Preventive Medicine, Mt. Sinai School of Medicine, One Gustave Levy Place, Box 1043, New York, New York 10029, USA
Breast Cancer Research 2006, 8:R71 doi:10.1186/bcr1629
Published: 20 December 2006Abstract
Introduction
The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk remains unclear. Inconsistencies in previously reported findings may be partly due to differences in expression of cyclooxygenase (COX)-2. We hypothesized that genetic polymorphisms (COX-2 .926, COX-2 .5209, and COX-2 .8473) may reduce overall breast cancer risk or risk for subtypes of breast cancer by modulating the inflammatory response and may interact with aspirin or any NSAID use.
Methods
We conducted a population-based, case-control study in which we genotyped 1,067 breast cancer cases and 1,110 control individuals included in the Long Island Breast Cancer Study Project.
Results
No major effects of the three COX-2 variant alleles on breast cancer risk were found. A total of eight distinct haplotypes and 18 diplotypes were observed in the population. Overall, no significant associations between COX-2 haplotypes/diplotypes and breast cancer risk were observed. Among women who used aspirin or any NSAID there was little evidence for an interaction with the at-risk COX-2 genotypes, with one exception. Among women with hormone receptor positive breast cancer, the reduced risk for any NSAID use was only evident among those who had at least one variant C allele of COX-2 .8473 (odds ratio = 0.7, 95% confidence interval = 0.5 to 1.0; P for the interaction = 0.02). There was no corresponding interaction for aspirin use, possibly because of limited power.
Conclusion
These data provide modest evidence that the C allele of COX-2 .8473 may interact with NSAIDs to reduce risk for hormone receptor positive breast cancer.