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

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. © 2006 Wiley‐Liss, Inc.