Genetic variation in the COX-2 gene and the association with prostate cancer risk

Int J Cancer. 2006 Aug 1;119(3):668-72. doi: 10.1002/ijc.21864.


COX-2 is a key enzyme in the conversion of arachidonic acid to prostaglandins. The prostaglandins produced by COX-2 are involved in inflammation and pain response in different tissues in the body. Accumulating evidence from epidemiologic studies, chemical carcinogen-induced rodent models and clinical trials indicate that COX-2 plays a role in human carcinogenesis and is overexpressed in prostate cancer tissue. We examined whether sequence variants in the COX-2 gene are associated with prostate cancer risk. We analyzed a large population-based case-control study, cancer prostate in Sweden (CAPS) consisting of 1,378 cases and 782 controls. We evaluated 16 single nucleotide polymorphisms (SNPs) spanning the entire COX-2 gene in 94 subjects of the control group. Five SNPs had a minor allele frequency of more than 5% in our study population and these were genotyped in all case patients and control subjects and gene-specific haplotypes were constructed. A statistically significant difference in allele frequency between cases and controls was observed for 2 of the SNPs (+3100 T/G and +8365 C/T), with an odds ratio of 0.78 (95% CI=0.64-0.96) and 0.65 (95% CI=0.45-0.94) respectively. In the haplotype analysis, 1 haplotype carrying the variant allele from both +3100 T/G and +8365 C/T, with a population frequency of 3%, was also significantly associated with decreased risk of prostate cancer (p=0.036, global simulated p-value=0.046). This study supports the hypothesis that inflammation is involved in prostate carcinogenesis and that sequence variation within the COX-2 gene influence the risk of prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Cyclooxygenase 2 / genetics*
  • Gene Frequency
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Humans
  • Incidence
  • Linkage Disequilibrium
  • Male
  • Membrane Proteins / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / genetics*
  • Risk Factors
  • Sweden / epidemiology


  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human