Investigation of Relationship Between Endothelial Nitric Oxide Synthase T786C Polymorphism and PSA, PSA Derivatives, and Prostate Cancer in Turkish Population
Endothelial NOS T786C Polymorphism in Prostate Cancer
Abstract
Background: Prostate cancer is a slowly progressing cancer seen in older men. Despite advances, prostate cancer remains a major medical problem for affected men. Risk factors of prostate cancer include age, race and prostate cancer family history. Prostate cancer may occur at different frequencies between ethnic populations and countries. Currently, studies on genetic risk factors in prostate cancer etiology have been increasing, and the results show that they are interrelated.
Nitric oxide synthase is the enzyme that converts L-arginine to Nitric Oxide. It has been shown that changes in endothelial nitric oxide synthase have an important role in carcinogenesis and the cardiovascular system. There are studies evaluating the relationship of endothelial nitric oxide synthase gene T786C polymorphism with prostate cancer risk in different populations and the results are contradictory.
Based on this, we aimed to reveal whether endothelial nitric oxide synthase T786C polymorphism exists in the participants and whether it was associated with prostate cancer.
Methods: Archival samples included in this study were whole blood samples taken from patients who were grouped according to prostate biopsy pathology results and from healty participants. DNA was isolated from these whole blood samples, and real-time polymerase chain reaction analysis was performed for endothelial nitric oxide synthase T786C polymorphism with LightCycler 480 II. Measured free and total prostate specific antigen serum levels were evaluated retrospectively.
Results: There was a statistically difference between patient-healthy control and control-healthy control groups in terms of genotype distributions for endothelial nitric oxide synthase T786C polymorphism. Healthy controls were more likely to have TC and CC genotypes, and C allele than the other two groups.
Conclusions: Contrary to the previous studies, in this study, no risk relationship was found between endothelial nitric oxide synthase T786C polymorphism and prostate cancer in the Turkish population.
References
2. Akbayır S, Muşlu N, Erden S, Bozlu M. Diagnostic value of microRNAs in prostate cancer patients with prostate specific antigen (PSA) levels between 2, and 10 ng/mL. Turk J Urol 2016;42(3):247-55.
3. Wang G, Zhao D, Spring DJ, DePinho RA. Genetics and biology of prostate cancer. Genes Dev 2018;32:1105–40.
4. Lee KM, Kang D, Park SK, Berndt SI, Reding D, Chatterjee N, et al. Nitric oxide synthase gene polymorphisms and prostate cancer risk. J Carcinog 2009;30(4):621–5.
5. Rebbeck RT. Prostate Cancer Genetics: Variation by Race, Ethnicity, and Geography. Semin Radiat Oncol 2017;27(1):3–10. doi:10.1016/j.semradonc.2016.08.002.
6. Smith RA, Mettlin CJ, Davis KJ, Eyre H. American Cancer Society Guidelines for the early detection of cancer. CA Cancer J Clin 2000;50:34-49.
7. Carroll P, Coley C, McLeod D, Schellhammer P, Sweat G, Wasson J, et al. Prostate specific antigen best practice policy- part I: Early detection and diagnosis of prostate cancer. Urology 2001;57(2):217-24. https://doi.org/10.1016/S0090-4295(00)00993-6.
8. Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, et al. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: Results of a multicenter clinical trial of 6630 men [abstract]. J Urol 1994;151(5);1283-90. DOI: 10.1016/s0022-5347(17)35233-3.
9. Abedinzadeh M, Dastgheib SA, Maleki H, Heiranizadeh N, Zare M, Jafari-Nedooshan J, et al. Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms with Susceptibility to Prostate Cancer: a Comprehensive Systematic Review and Meta-Analysis. Urol J 2020;17(4):329-37.
10. Ziaei SAM, Samzadeh M, Jamaldini SH, Afshari M, Haghdoost AA, Hasanzad M. Endothelial nitric oxide synthase Glu298Asp polymorphism as a risk factor for prostate cancer. Int J Biol Markers 2013;28(1):43-8.
11. Medeiros R, Morais A, Vasconcelos A, Costa S, Pinto D, Oliveira J, et al. Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer [abstract]. Eur J Cancer Prev 2002;11(4):343-50. doi: 10.1097/00008469-200208000-00005.
12. Wang XL, Mahaney MC, Sim AS, Wang J, Wang J, Blangero J, et al. Genetic contribution of the endothelial constitutive nitric oxide synthase gene to plasma nitric oxide. Arterioscler Thromb Vasc Biol 1997;17(11):3147-53. doi: 10.1161/01.atv.17.11.3147.
13. Diler SB, Öden A. The T786C, G894T, and Intron 4 VNTR (4a/b) Polymorphisms of the Endothelial Nitric Oxide Synthase Gene in Prostate Cancer Cases [abstract]. Genetika 2016;52(2):249-54. doi: 10.7868/s0016675816020028.
14. Safarinejad MR, Safarinejad S, Shafiei N, Safarinejad S. Effects of the T786C, G894T, and Intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene on the risk of prostate cancer [abstract]. Urol Oncol 2013;31:1132-40.
15. Zhang L, Chen LM, Wang MN, Chen XJ, Li N, Huang YD, et al. The G894T, T‐786C and 4b/a polymorphisms in Enos gene and cancer risk: a meta‐analysis [abstract]. J Evid Based Med 2014;7(4):263-9. doi: 10.1111/jebm.12126.
16. Majumdar V, Nagaraja D, Karthik N, Christopher R. Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms with Early-Onset Ischemic Stroke in South Indians. J Atheroscler Thromb 2010;17:45-53.
17. Wu X, Wang ZF, Xu Y, Ren R, Heng BL, Su ZX. Association Between Three eNOS Polymorphisms and Cancer Risk: a Meta-analysis. Asian Pac J Cancer Prev 2014;15:5317-24.
18. Orabi H, Albersen M, Lue TF. Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management. Int J Impot Res 2011;23(3):99-108. doi: 10.1038/ijir.2011.14.
19. Chinje EC, Stratford IJ. Role of nitric oxide in growth of solid tumours: a balancing act. Essays Biochem 1997;32:61-72.
20. Gauthier N, Arnould L, Chantome A, Reisser D, Bettaieb A, Reveneau S, et al. To stimulate or to inhibit nitric oxide production in mammary tumors? Bull Cancer 2004;91(9):705–12.
21. Wamvakas S, Schmidt HH. Just say NO to cancer? J Natl Cancer Inst 1997;89(6):406-7. doi: 10.1093/jnci/89.6.406.
22. Lejeune P, Lagadec P, Onier N, Pinard D, Ohshima H, Jeannin JF. Nitric oxide involvement in tumor-induced immunosuppression [abstract]. J Immunol 1994;152(10):5077-83.
23. İşman FK, Balcı MBC, Hazar İ, Yılmaz İ, Fettahoğlu F. BPH ve Prostat Kanserinde PSA ile Kan Nitrik Oksit (NO) Değerlerinin Korelasyonu. Turk J Urol 2004;30(4):410-3.
Copyright (c) 2022 Senay BALCI, Serin AKBAYIR, Murat BOZLU, Lulufer TAMER
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