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Protective effect of NSAIDs on cancer and influence of COX-2 C(-765G) genotype

C Siemes1, L E Visser, J W W Coebergh

  • 1Department of Epidemiology & Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands. b.stricker@erasmusmc.nl

Current Cancer Drug Targets
|December 17, 2008
PubMed
Abstract

Insights

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal cancer risk. Colorectal cancer patients with a COX-2 C(-765) allele who use NSAIDs show improved survival compared to wild-type non-users.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) are hypothesized to impact carcinogenesis via cyclooxygenase-2 (COX-2) inhibition.
  • The role of NSAID use and its interaction with COX-2 genetic variations in cancer development and outcomes requires further elucidation.

Purpose of the Study:

  • To investigate the association between cumulative NSAID use and the risk of four common cancers (colorectal, lung, breast, prostate).
  • To examine the modifying effect of the COX-2 G(-765)C single nucleotide polymorphism on cancer risk and survival.
  • To assess the impact of NSAID use in combination with COX-2 genotype on survival outcomes.

Main Methods:

  • The Rotterdam Study cohort, including 7621 participants, was analyzed over a mean follow-up of 10 years.
  • Cox's proportional hazard models were used to evaluate the associations of NSAID use and COX-2 genotype with cancer incidence and mortality.
  • NSAID use was categorized by drug class, and analyses were stratified by COX-2 genotype.

Main Results:

  • NSAID use across all classes was linked to a reduced risk of colorectal cancer, but not other studied cancers.
  • No significant associations were found between the COX-2 G(-765)C genotype and cancer incidence or mortality.
  • COX-selective NSAIDs demonstrated a modest additional risk reduction for colorectal cancer.
  • Colorectal cancer patients who were carriers of the COX-2 C(-765) allele and had used NSAIDs in the five years prior to diagnosis exhibited more than double the survival time compared to wild-type homozygous non-users (p = 0.007).

Conclusions:

  • NSAID use is confirmed to have a protective effect against colorectal cancer development.
  • Individuals with colorectal cancer carrying a COX-2 C(-765) allele who use NSAIDs experience improved survival compared to non-users with the wild-type genotype.

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