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Carcinogenesis Advance Access originally published online on October 28, 2008
Carcinogenesis 2008 29(12):2347-2350; doi:10.1093/carcin/bgn245
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

COX-2 promoter polymorphisms and the association with prostate cancer risk in South African men

Pedro Fernandez1,*, Pieter M. de Beer1,2, Lize van der Merwe3,4 and Chris F. Heyns1,2

1 Department of Urology, Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa
2 Department of Urology, Tygerberg Hospital, Tygerberg 7505, South Africa
3 Biostatistics Unit, Medical Research Council, PO Box 17090, Tygerberg, 7505, South Africa
4 Department of Statistics, University of the Western Cape, Private Bag X17, Bellville, 7535, South Africa

* To whom correspondence should be addressed. Tel: +27 21 938 9288; Fax: +27 21 933 8010; Email: pf3{at}sun.ac.za

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.

Abbreviations: C/EBP, CCAAT/enhancer-binding protein; CI, confidence interval; COX-2, cyclooxygenase-2; OR, odds ratio; SNP, single-nucleotide polymorphism

Received June 8, 2008; revised October 16, 2008; accepted October 23, 2008.


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