Protective effect of nonsteroidal anti-inflammatory drugs on colorectal adenomas is modified by a polymorphism in peroxisome proliferator-activated receptor [Delta]

C.L.E. Siezen, M.J. Tijhuis, N.R. Kram, E.M. van Soest, D.J. de Jong, R. Fodde, H.J. Kranen, E. Kampman

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)

Abstract

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a decreased risk of colorectal tumors. Single nucleotide polymorphisms (SNPs) in target genes of NSAID action, and their haplotypes, might modulate this protective effect. METHODS: A case-control study including 724 cases and 682 controls was used to evaluate the effect of NSAIDs on colorectal adenoma risk in The Netherlands, a country in which NSAID use is relatively low. Cases and controls were classified according to presence or absence of endoscopy-proven, pathology-confirmed colorectal adenomas, ever in their lives. Thirteen SNPs in four genes (PPARdelta, PPARgamma, PTGS1 and PTGS2) were genotyped in 787 subjects (384 cases and 403 controls). RESULTS: Compared to non-regular users (<12 times/year), regular users of NSAIDs (> or = 12 times/year) had a lower risk of colorectal adenomas (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.56-0.99). The results were similar for aspirin only. We found an interaction between SNP c.-789C>T in PPARdelta and NSAID use (P=0.03). The protective effect of NSAIDs was strengthened for regular users with the PPARdelta CT or TT genotypes (OR: 0.35, 95%CI: 0.11-1.13), whereas a positive association was observed for non-regular users with these genotypes (OR: 2.24, 95%CI: 1.06-4.73) as compared to non-regular users with the CC genotype. Also, a statistically significant interaction between a major haplotype containing the minor allele of this SNP and NSAID use was observed. CONCLUSIONS: This study confirms the protective effect of NSAIDs and suggests a modulating effect of a SNP in the promoter of PPARdelta.
Original languageEnglish
Pages (from-to)43-50
JournalPharmacogenetics and Genomics
Volume16
Issue number1
DOIs
Publication statusPublished - 2006

Keywords

  • cyclooxygenase-2 inhibitor
  • cancer
  • risk
  • chemoprevention
  • consumption
  • rofecoxib
  • carcinoma
  • polyposis
  • target
  • growth

Fingerprint Dive into the research topics of 'Protective effect of nonsteroidal anti-inflammatory drugs on colorectal adenomas is modified by a polymorphism in peroxisome proliferator-activated receptor [Delta]'. Together they form a unique fingerprint.

  • Cite this