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

Breast Cancer Res. 2006;8(6):R71. doi: 10.1186/bcr1629.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / therapeutic use*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / prevention & control*
  • Case-Control Studies
  • Cyclooxygenase 2 / genetics*
  • Female
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide
  • Receptors, Steroid
  • Risk

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Receptors, Steroid
  • Cyclooxygenase 2
  • Aspirin