Abstract
Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression, and metastasis. We aimed to evaluate the association between COX-2 (rs2745557) polymorphism and prostate cancer (PCa), benign prostate hyperplasia (BPH) risk. We also assessed the influence of other risk factors such as obesity, smoking, diabetes in modulating the risk of PCa in Egyptian men. COX-2 (rs2745557) was genotyped in 112 PC patients, 111 BPH and 120 subjects as a control group. COX-2 and PSA levels were measured by ELISA. We found that GG genotype was associated with a 17-fold increased risk for PCa and 20-fold increased the risk for BPH more than AA genotype. Also, G allele carriers of COX-2 were associated with metastatic cancer (OR = 1.3, P < 0.05) and disease aggressiveness (OR = 3.5, P < 0.001). The coexistence of obesity, smoking, or diabetes with GG genotype may lead to increasing the risk of developing BPH (OR = 3.3, 4, and 2.7, respectively) and of developing PCa (OR = 2.9, 4.9, and 3.2, respectively). Our results showed evidence suggesting the involvement of the COX-2 (rs2745557) polymorphism and its protein in PCa or BPH initiation and progression. Also, the coexistence of COX-2 (rs2745557) and obesity, smoking, or diabetes may lead to the development of PCa or BPH.
Similar content being viewed by others
References
Alcaraz A, Hammerer P, Tubaro A, Schroder FH, Castro R (2009) Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review. Eur Urol 55:864–875
Amirian ES, Ittmann MM, Scheurer ME (2011) Associations between arachidonic acid metabolism gene polymorphisms and prostate cancer risk. Prostate 71:1382–1389
Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J et al (2004) Human prostate cancer risk factors. Cancer 101:2371–2490
Cao Y, Prescott SM (2002) Many actions of cyclooxygenase-2 in cellular dynamics and in cancer. J Cell Physiol 190:279–286
Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O et al (2012) International variation in prostate cancer incidence and mortality rates. Eur Urol 61:1079–1092
Cheng I, Liu X, Plummer SJ, Krumroy LM, Casey G, Witte JS (2007) COX2 genetic variation, NSAIDs, and advanced prostate cancer risk. Br J Cancer 97:557–561
Dossus L, Kaaks R, Canzian F, Albanes D, Berndt SI, Boeing H et al (2010) PTGS2 and IL6 genetic variation and risk of breast and prostate cancer: results from the Breast and Prostate Cancer Cohort Consortium (BPC3). Carcinogenesis 31:455–461
Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB et al (1998) Cyclooxygenase in biology and disease. FASEB J 12:1063–1073
Edwards SM, Eeles RA (2004) Unravelling the genetics of prostate cancer. Am J Med Genet C 129:65–73
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC Cancer Base no. 10 [Internet]. International Agency for Research on Cancer, Lyon
Floriano-Sánchez E, Torres-Salazar JJ, Cárdenas-Rodríguez N, Castro-Marín M, Zapata-Villalba MA, Flores Terrazas JE (2010) Cyclooxigenase-2 (COX-2) expression determination in prostate cancer and benign prostatic hyperplasia tissue. Rev Mex Urol 70(3):137–140
Hara N, Kitamura Y, Saito T, Komatsubara S (2006) Total and free prostate-specific antigen Indexes in prostate cancer screening: value and limitation for Japanese populations. Asian J Androl 8:429–434
Helpap B, Egevad L (2009) Modified Gleason grading. An updated review. Histol Histopathol 24:661–666
Herschman HR (1995) Prostaglandin synthase 2. Biochim Biophys Acta 1299:125–140
Howell WM, Rose-Zerilli MJ (2007) Cytokine gene polymorphisms, cancer susceptibility, and prognosis. J Nutr 137:194S–199S
Huncharek M, Haddock KS, Reid R, Kupelnick B (2010) Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. Am J Public Health 100:693–701
Jani AB, Hellman S (2003) Early prostate cancer: clinical decision-making. Lancet 361:1045–1053
Khodier MM, Mohmoud SA, Gabal SM, Abou-Sriea MA (2009) Cyclooxygenase-2 (COX-2) expression in Egyptian cases of benign prostatic hyperplasia and prostatic adenocarcinoma. Acad J Cancer Res 2(1):33–39
Lee LM, Pan CC, Cheng CJ, Chi CW, Liu TY (2001) Expression of cyclooxygenase-2 in prostate adenocarcinoma and benign prostatic hyperplasia. Anticancer Res 21:1291–1294
Lee SH, Williams MV, Dubois RN, Blair IA (2005) Cyclooxygenase-2-mediated DNA damage. J Biol Chem 280:28337–28346
Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M et al (2000) Environmental and heritable factors in the causation of cancer: analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–84
Lopergolo A, Zaffaroni N (2009) Biomolecular markers of outcome prediction in prostate cancer. Cancer 115:3058–3067
Mandal RK, Mittal RD (2011) Polymorphisms in COX-2 gene influence prostate cancer susceptibility in a northern Indian cohort. Arch Med Res 42:620–626
Panguluri RC, Long LO, Chen W, Wang S, Coulibaly A, Ukoli F et al (2004) COX-2 gene promoter haplotypes and prostate cancer risk. Carcinogenesis 25:961–966
Shahedi K, Lindstrom S, Zheng SL, Wiklund F, Adolfsson J, Sun J et al (2006) Genetic variation in the COX-2 gene and the association with prostate cancer risk. Int J Cancer 119:668–672
Shalaby MA, Nounou HA, Alanazi MS, Alharby O, Azzam N, Saeed HM (2014) Associations between single nucleotide polymorphisms of COX-2 and MMP-2 genes and colorectal cancer susceptibility in the Saudi population. Asian Pac J Cancer Prev 15:4989–4994
Shao N, Feng N, Wang Y, Mi Y, Li T, Hua L (2012) Systematic review and meta-analysis of COX-2 expression and polymorphisms in prostate cancer. Mol Biol Rep 39:10997–11004
St Sauver JL, Lieber MM, Slager SL, Jacobson DJ, McGree ME, Jacobsen SJ (2011) Associations between variants in the cyclooxygenase 2 enzyme gene (PTGS2) and development of benign prostate enlargement. BJU Int 108:1610–1615
Subbarayan V, Sabichi AL, Llansa N, Lippman SM, Menter DG (2001) Differential expression of cyclooxygenase-2 and its regulation by tumor necrosis factor-alpha in normal and malignant prostate cells. Cancer Res 61:2720–2726
Sugie S, Tsukino H, Mukai S, Akioka T, Shibata N, Nagano M et al (2013) Cyclooxygenase 2 genotypes influence prostate cancer susceptibility in Japanese Men. Tumour Biol 35(3):2717–2721
Wu HC, Chang CH, Ke HL, Chang WS, Cheng HN, Lin HH et al (2011) Association of cyclooxygenase 2 polymorphic genotypes with prostate cancer in taiwan. Anticancer Res 31:221–225
Zhang H, Xu Y, Zhang Z, Liu R, Ma B (2012) Association between COX-2 rs2745557 polymorphism and prostate cancer risk: a systematic review and meta-analysis. BMC Immunol 13:14
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None of the authors have any competing interests in the manuscript.
Rights and permissions
About this article
Cite this article
Fawzy, M.S., Elfayoumi, AR., Mohamed, R.H. et al. Cyclooxygenase 2 (rs2745557) Polymorphism and the Susceptibility to Benign Prostate Hyperplasia and Prostate Cancer in Egyptians. Biochem Genet 54, 326–336 (2016). https://doi.org/10.1007/s10528-016-9722-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-016-9722-4