Carcinogenesis Advance Access originally published online on January 30, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 25, No. 6, 961-966,
June 2004
Carcinogenesis vol.25 no.6 © Oxford University Press 2004; all rights reserved.
ARTICLE |
COX-2 gene promoter haplotypes and prostate cancer risk
1 National Human Genome Center at Howard University, 2 Divison of Urology, Howard University Hospital and 3 Howard University Cancer Center, Washington, DC 20060, USA, 4 National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arizona, USA, 5 School of Nursing, University of Louisville, Louisville, KY 40292, USA and 6 Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
7 To whom correspondence should be addressed Email: rkittles{at}howard.edu
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/EBP
) and NF-
B 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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Fradet, I. Cheng, G. Casey, and J. S. Witte Dietary Omega-3 Fatty Acids, Cyclooxygenase-2 Genetic Variation, and Aggressive Prostate Cancer Risk Clin. Cancer Res., April 1, 2009; 15(7): 2559 - 2566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fernandez, P. M. de Beer, L. van der Merwe, and C. F. Heyns COX-2 promoter polymorphisms and the association with prostate cancer risk in South African men Carcinogenesis, December 1, 2008; 29(12): 2347 - 2350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. N. Danforth, R. B. Hayes, C. Rodriguez, K. Yu, L. C. Sakoda, W.-Y. Huang, B. E. Chen, J. Chen, G. L. Andriole, E. E. Calle, et al. Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case-control studies Carcinogenesis, March 1, 2008; 29(3): 568 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, F. R. Schumacher, S. J. Plummer, E. Jorgenson, G. Casey, and J. S. Witte trans-Fatty acid intake and increased risk of advanced prostate cancer: modification by RNASEL R462Q variant Carcinogenesis, June 1, 2007; 28(6): 1232 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Sakoda, Y.-T. Gao, B. E. Chen, J. Chen, P. S. Rosenberg, A. Rashid, J. Deng, M.-C. Shen, B.-S. Wang, T.-Q. Han, et al. Prostaglandin-endoperoxide synthase 2 (PTGS2) gene polymorphisms and risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China Carcinogenesis, June 1, 2006; 27(6): 1251 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R A Kittles, A B Baffoe-Bonnie, T Y Moses, C M Robbins, C Ahaghotu, P Huusko, C Pettaway, S Vijayakumar, J Bennett, G Hoke, et al. A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history J. Med. Genet., June 1, 2006; 43(6): 507 - 511. [Abstract] [Full Text] [PDF]
|
|