Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk.
BACKGROUND
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.


CONCLUSIONS
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.
Shen
Jing
J
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 630 West 168th Street, New York, New York 10032, USA. js2182@columbia.edu
Gammon
Marilie D
MD
Terry
Mary Beth
MB
Teitelbaum
Susan L
SL
Neugut
Alfred I
AI
Santella
Regina M
RM
D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011987:Receptors, Steroid; D012306:Risk
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011987:Receptors, Steroid; D051546:Cyclooxygenase 2; D001241:Aspirin