TY - JOUR
T1 - COX-2 gene promoter haplotypes and prostate cancer risk
AU - Panguluri, Ramesh C.K.
AU - Long, Layron O.
AU - Chen, Weidong
AU - Wang, Songping
AU - Coulibaly, Aoua
AU - Ukoli, Flora
AU - Jackson, Aaron
AU - Weinrich, Sally
AU - Ahaghotu, Chiledum
AU - Isaacs, William
AU - Kittles, Rick A.
N1 - Funding Information:
We thank all volunteers who participated in this study. We appreciate the assistance of K.Joseph and Drs U.Osime and F.Akenyeni in subject enrollment and data management. We also thank Dr C.Bonilla and two anonymous reviewers for helpful comments on the manuscript. This work was supported by NIH (RR03048-13S1 and 1U54CA91431-01), the Department of Defense (DAMD17-00-1-0025 and DAMD 17-02-1-0067), and the Howard University Cancer Center.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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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U2 - 10.1093/carcin/bgh100
DO - 10.1093/carcin/bgh100
M3 - Article
C2 - 14754878
AN - SCOPUS:3042853949
SN - 0143-3334
VL - 25
SP - 961
EP - 966
JO - Carcinogenesis
JF - Carcinogenesis
IS - 6
ER -