title: COX-2 promoter polymorphisms and the association with prostate cancer risk in South African men.
abstract: Cyclooxygenase-2 (COX-2) converts arachidonic acid to prostaglandins, which are important mediators of cell proliferation and inflammation. Evidence indicates that COX-2 plays a role in carcinogenesis and that it is over-expressed in prostate tumours. We investigated the role of COX-2 variants in prostate cancer in a case-control study of South African Coloured men, consisting of 151 cases and 134 controls. The genotype frequencies of four single-nucleotide polymorphisms (SNPs) in the COX-2 promoter were initially determined in 50 control subjects. One SNP, rs20417 (-899G>C), was monomorphic and excluded from further investigation. Three SNPs, rs3918304 (-1285A>G), rs20415 (-1265C>T) and rs5270 (-297C>G), were genotyped in all the case patients and control subjects. The -1285 G-allele and -1265 T-allele were associated with increased risk of prostate cancer [odds ratio (OR) = 3.53; confidence interval (CI) = 2.14-5.90; P < 0.0001 and OR = 3.01; CI = 1.82-5.02; P < 0.0001] after adjusting for age. Haplotype GTC conferred increased risk of prostate cancer in South African Coloured men (OR = 3.54 versus ACC; CI = 2.12-5.92; P < 0.0001). These findings in conjunction with findings in other populations of African descent might suggest a common causal variant for prostate cancer in COX-2, or a variant in a nearby gene.
authors.affiliation: Department of Urology, Stellenbosch University, Tygerberg, South Africa. pf3@sun.ac.za
authors.forename: Pedro
authors.initials: P
authors.lastname: Fernandez
authors.forename: Pieter M
authors.initials: PM
authors.lastname: de Beer
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Chris F
authors.initials: CF
authors.lastname: Heyns
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D013019:South Africa
chemical_list: D051546:Cyclooxygenase 2