COX-2 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 B Isaacs, Rick A. Kittles

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)961-966
Number of pages6
JournalCarcinogenesis
Volume25
Issue number6
DOIs
StatePublished - Jun 2004

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Cyclooxygenase 2
Haplotypes
Prostatic Neoplasms
Odds Ratio
African Americans
Single Nucleotide Polymorphism
Genes
Genetic Promoter Regions
Binding Sites
CCAAT-Enhancer-Binding Protein-alpha
Microvessels
Arachidonic Acid
Population
Prostaglandins
Case-Control Studies
Neoplasms
Transcription Factors
High Pressure Liquid Chromatography
Apoptosis
Neoplasm Metastasis

ASJC Scopus subject areas

  • Cancer Research

Cite this

Panguluri, R. C. K., Long, L. O., Chen, W., Wang, S., Coulibaly, A., Ukoli, F., ... Kittles, R. A. (2004). COX-2 gene promoter haplotypes and prostate cancer risk. Carcinogenesis, 25(6), 961-966. https://doi.org/10.1093/carcin/bgh100

COX-2 gene promoter haplotypes and prostate cancer risk. / Panguluri, Ramesh C K; Long, Layron O.; Chen, Weidong; Wang, Songping; Coulibaly, Aoua; Ukoli, Flora; Jackson, Aaron; Weinrich, Sally; Ahaghotu, Chiledum; Isaacs, William B; Kittles, Rick A.

In: Carcinogenesis, Vol. 25, No. 6, 06.2004, p. 961-966.

Research output: Contribution to journalArticle

Panguluri, RCK, Long, LO, Chen, W, Wang, S, Coulibaly, A, Ukoli, F, Jackson, A, Weinrich, S, Ahaghotu, C, Isaacs, WB & Kittles, RA 2004, 'COX-2 gene promoter haplotypes and prostate cancer risk', Carcinogenesis, vol. 25, no. 6, pp. 961-966. https://doi.org/10.1093/carcin/bgh100
Panguluri RCK, Long LO, Chen W, Wang S, Coulibaly A, Ukoli F et al. COX-2 gene promoter haplotypes and prostate cancer risk. Carcinogenesis. 2004 Jun;25(6):961-966. https://doi.org/10.1093/carcin/bgh100
Panguluri, Ramesh C K ; Long, Layron O. ; Chen, Weidong ; Wang, Songping ; Coulibaly, Aoua ; Ukoli, Flora ; Jackson, Aaron ; Weinrich, Sally ; Ahaghotu, Chiledum ; Isaacs, William B ; Kittles, Rick A. / COX-2 gene promoter haplotypes and prostate cancer risk. In: Carcinogenesis. 2004 ; Vol. 25, No. 6. pp. 961-966.
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abstract = "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.",
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