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Carcinogenesis Advance Access published online on October 28, 2008
Carcinogenesis, 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 de Beer1,2, Lize van der Merwe3,4 and Christiaan Heyns1,2

1 Stellenbosch University, Department of Urology, Tygerberg, South Africa
2 Tygerberg Hospital, Department of Urology, Tygerberg, South Africa
3 Biostatistics Unit, Medical Research Council of South Africa, Tygerberg, South Africa
4 Department of Statistics, University of the Western Cape, Bellville, South Africa

Corresponding author: Pedro Fernandez, Stellenbosch University, Department of Urology, P O Box 19063, Tygerberg, 7505, South Africa, Fax: +27 21 933 8010, Fax (alternate): +27 21 931 7810, 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 (OR = 3.53; 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.

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


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