Journal Article

<i>COX-2</i> gene promoter haplotypes and prostate cancer risk

Ramesh C.K. Panguluri, Layron O. Long, Weidong Chen, Songping Wang, Aoua Coulibaly, Flora Ukoli, Aaron Jackson, Sally Weinrich, Chiledum Ahaghotu, William Isaacs and Rick A. Kittles

in Carcinogenesis

Volume 25, issue 6, pages 961-966
Published in print June 2004 | ISSN: 0143-3334
Published online June 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh100
COX-2 gene promoter haplotypes and prostate cancer risk

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Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflamatory prostaglandins. COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high-performance liquid chromatography. Four single nucleotide polymorphisms (SNPs), −1285A/G, −1265G/A, −899G/C and −297C/G, were detected and confirmed by direct sequencing. Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate CCAAT/enhancer binding protein alpha (C/EBPα) and NF-κB binding sites. A case-control study of the four SNPs in African American (n = 288), Bini Nigerian (n = 264) and European American (n = 184) prostate cancer cases and age-matched controls revealed that SNP −297G was associated with a decreased risk for prostate cancer [odds ratio (OR) = 0.49; CI = 0.2–0.9; P = 0.01]. The effect on risk was observed in both African Americans (OR = 0.51; CI = 0.2–0.9; P = 0.01) and European Americans (OR = 0.33; CI = 0.1–0.9; P = 0.02). In addition, SNPs −1265A and −899C were associated with increased prostate cancer risk in African Americans (OR = 2.72; CI = 1.3–5.8; P = 0.007 and OR = 3.67; CI = 1.4–9.9; P = 0.007, respectively). Haplotype analyses revealed modest effects on susceptibility to prostate cancer across populations. Haplotype GGCC conferred increased risk in the African American and Nigerian populations. Conversely, haplotype AGGG exhibited a negative association with prostate cancer risk in African Americans (OR = 0.4; CI = 0.1–0.9; P = 0.02) and European Americans (OR = 0.2; CI = 0.1–0.9; P = 0.03). These data suggest that variation of the COX-2 promoter may influence the risk and development of prostate cancer.

Keywords: C/EBPα, CCAAT/enhancer binding protein alpha; COX, cyclooxygenase; DRE, digital rectal exam; PSA, prostate specific antigen; SNPs, single nucleotide polymorphisms; TNM, tumor node metastasis

Journal Article.  4969 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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