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Determination of the Roles of Endothelial Nitric Oxide Synthase 4VNTR (4a/b), G894T, T786C Gene Variations in the Bladder Cancer Development

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Abstract

The aim of this study is to determine the roles of eNOS gene variations in BCA development. Our study included 91 patients diagnosed with BCA and 91 healthy controls. eNOS 4VNTR (4a/b), T786C and G894T gene variations genotype distributions were determined by PCR and RFLP methods. The significant difference was determined between these groups in terms of eNOS T786C and eNOS G894T gene variations genotype distributions (p < 0.05). TT genotype for G894T gene variation and CC genotype for T786C gene variation were detected higher in patients. The CC genotype of T786C gene variation was detected significantly higher in male patients than in male controls (p < 0.05). In addition, aa-TT, ab-TT, bb-TT haplotypes of 4VNTR (4a/b)-G894T gene variations, aa-CC, ab-CC, bb-CC haplotypes of 4VNTR (4a/b)-T786C gene variations and TT-TT, TT-CC, TT-CT, GG-CC, GT-CC haplotypes of G894T-T786C gene variations were observed in patient group more than control group. The significant difference was detected between these groups in terms of eNOS (G894T-T786C) haplotypes (p < 0.05). In our study, eNOS T786C and eNOS G894T gene variations were determined important genetic risk factor in the Thrace population of Turkey.

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References

  1. Toker A, Erkan E, Hocaoglu Emre FS, Yucetas U. eNOS gene polymorphisms and transitional cell cancer of the bladder. Ann Med Res. 2020;27(7):2004–10. https://doi.org/10.5455/annalsmedres.2020.01.039.

    Article  Google Scholar 

  2. Nan J, Liu Y, Xu C, Ge D. Effects of eNOS gene polymorphisms on individual susceptibility to cancer: a meta-analysis. Nitric Oxide. 2019;84:1–6. https://doi.org/10.1016/j.niox.2018.12.006.

    Article  CAS  PubMed  Google Scholar 

  3. Polat F, Diler SB, Azazi İ, Öden A. T-786C, G894T, and intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in bladder cancer cases. Asian Pac J Cancer Prev. 2015;16(6):2199–202. https://doi.org/10.7314/apjcp.2015.16.6.2199.

    Article  PubMed  Google Scholar 

  4. Salimian Rizi B, Achreja A, Nagrath D. Nitric oxide: the forgotten child of tumor metabolism. Trends Cancer. 2017;3(9):659–72. https://doi.org/10.1016/j.trecan.2017.07.005.

    Article  CAS  PubMed  Google Scholar 

  5. Luanpitpong S, Chanvorachote P. Nitric oxide and aggressive behavior of lung cancer cells. Anticancer Res. 2015;35(9):4585–92.

    CAS  PubMed  Google Scholar 

  6. Burke AJ, Sullivan FJ, Giles FJ, Glynn SA. The yin and yang of nitric oxide in cancer progression. Carcinogenesis. 2013;34(3):503–12. https://doi.org/10.1093/carcin/bgt034.

    Article  CAS  PubMed  Google Scholar 

  7. Choudhari SK, Chaudhary M, Bagde S, Gadbail AR, Joshi V. Nitric oxide and cancer: a review. World J Surg Oncol. 2013;30(11):118. https://doi.org/10.1186/1477-7819-11-118.

    Article  Google Scholar 

  8. Raina P, Sikka R, Gupta H, Matharoo K, Bali SK, Singh V, et al. Association of eNOS and MCP-1 genetic variants with type 2 diabetes and diabetic nephropathy susceptibility: a case-control and meta-analysis study. Biochem Genet. 2021;59(4):966–96. https://doi.org/10.1007/s10528-021-10041-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Abbasi H, Dastgheib SA, Hadadan A, Karimi-Zarchi M, Javaheri A, Meibodi B, et al. Association of endothelial nitric oxide synthase 894G > T polymorphism with preeclampsia risk: a systematic review and meta-analysis based on 35 studies. Fetal Pediatr Pathol. 2021;40(5):455–70. https://doi.org/10.1080/15513815.2019.1710880.

    Article  PubMed  Google Scholar 

  10. Bayraktutan Z, Kiziltunc A, Bakan E, Alp HH. Determination of endothelial nitric oxide synthase gene polymorphism and plasma asymmetric dimethyl arginine concentrations in patients with lung cancer. Eurasian J Med. 2020;52(2):185–90. https://doi.org/10.5152/eurasianjmed.2020.19220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Adibmanesh A, Bijanzadeh M, Mohammadzadeh G, Alidadi R, Rashidi M, Talaizadeh A. The correlation of endothelial nitric oxide synthase gene rs1799983 polymorphisms with colorectal cancer. Int J Cancer Manag. 2020;13(5):e97220. https://doi.org/10.5812/ijcm.97220.

    Article  Google Scholar 

  12. 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. https://doi.org/10.22037/uj.v0i0.5445.

    Article  PubMed  Google Scholar 

  13. Azuma S, Uojima H, Chuma M, Shao X, Hidaka H, Nakazawa T, et al. Influence of NOS3 rs2070744 genotypes on hepatocellular carcinoma patients treated with lenvatinib. Sci Rep. 2020;10(1):17054. https://doi.org/10.1038/s41598-020-73930-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ay A, Alkanli N, Cevik G. Investigation of the relationship between MMP-1 (-1607 1G/2G), MMP-3 (-1171 5A/6A) gene variations and development of bladder cancer. Mol Biol Rep. 2021;48:7689–95. https://doi.org/10.1007/s11033-021-06775-2.

    Article  CAS  PubMed  Google Scholar 

  15. Günel T, Göksever Çelik H, Diz Kücükkaya R, Alkaç İM, Aydınlı K. Molecular mechanisms of endothelial function and dysfunction in human diseases. İKSSTD. 2020;12(3):201–16. https://doi.org/10.5222/iksstd.2020.61587.

    Article  Google Scholar 

  16. Tsay MD, Hsieh MJ, Wang SS, Wang WC, Chou YY, Shih CH, Yang SF, Chou YE. Impact of endothelial nitric oxide synthase polymorphisms on urothelial cell carcinoma development. Urol Oncol. 2019;37(4):293.e1-293.e9. https://doi.org/10.1016/j.urolonc.2018.12.023.

    Article  CAS  PubMed  Google Scholar 

  17. Ying L, Hofseth LJ. An emerging role for endothelial nitric oxide synthase in chronic inflammation and cancer. Cancer Res. 2007;67(4):1407–10. https://doi.org/10.1158/0008-5472.CAN-06-2149.

    Article  CAS  PubMed  Google Scholar 

  18. Oliveira-Paula GH, Lacchini R, Tanus-Santos JE. Clinical and pharmacogenetic impact of endothelial nitric oxide synthase polymorphisms on cardiovascular diseases. Nitric Oxide. 2017;63:39–51. https://doi.org/10.1016/j.niox.2016.08.004.

    Article  CAS  PubMed  Google Scholar 

  19. Levine AB, Punihaole D, Levine TB. Characterization of the role of nitric oxide and its clinical applications. Cardiology. 2012;122(1):55–68. https://doi.org/10.1159/000338150.

    Article  CAS  PubMed  Google Scholar 

  20. Dhananjayan R, Koundinya KS, Malati T, Kutala VK. Endothelial dysfunction in type 2 diabetes mellitus. Indian J Clin Biochem. 2016;31(4):372–9. https://doi.org/10.1007/s12291-015-0516-y.

    Article  CAS  PubMed  Google Scholar 

  21. Eghlim FF, Ashavaid TF, Nair KG. Genetic determinants of hyperhomocysteinemia in atherosclerosis. Indian J Clin Biochem. 2006;21(2):4–11. https://doi.org/10.1007/BF02912904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rishiraj U, Rohilla S, Kaur S. Correlation between intron 4 polymorphism of the endothelial nitric oxide synthase gene and cardiovascular risk with the numbers of circulating endothelial progenitor cells in healthy subjects. Indian J Clin Biochem. 2018;33(2):202–7. https://doi.org/10.1007/s12291-017-0662-5.

    Article  CAS  PubMed  Google Scholar 

  23. Amasyali AS, Kucukgergin C, Erdem S, Sanli O, Seckin S, Nane I. Nitric oxide synthase (eNOS4a/b) gene polymorphism is associated with tumor recurrence and progression in superficial bladder cancer cases. J Urol. 2012;188(6):2398–403. https://doi.org/10.1016/j.juro.2012.07.096.

    Article  CAS  PubMed  Google Scholar 

  24. Arıkan S, Cacina C, Guler E, Çulcu S, Tuna G, Yaylım-Eraltan I. The effects of NOS3 Glu298Asp variant on colorectal cancer risk and progression in Turkish population. Mol Biol Rep. 2012;39(3):3245–9. https://doi.org/10.1007/s11033-011-1092-8.

    Article  CAS  PubMed  Google Scholar 

  25. Lembo G, De Luca N, Battagli C, Iovino G, Aretini A, Musicco M, et al. A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis. Stroke. 2001;32(3):735–40. https://doi.org/10.1161/01.str.32.3.735.

    Article  CAS  PubMed  Google Scholar 

  26. Verim L, Toptas B, Ozkan NE, Cacina C, Turan S, Korkmaz G, et al. Possible relation between the NOS3 gene GLU298ASP polymorphism and bladder cancer in Turkey. Asian Pac J Cancer Prev. 2013;14(2):665–8. https://doi.org/10.7314/apjcp.2013.14.2.665.

    Article  PubMed  Google Scholar 

  27. Ryk C, Wiklund NP, Nyberg T, de Verdier PJ. Polymorphisms in nitric-oxide synthase 3 may influence the risk of urinary-bladder cancer. Nitric Oxide. 2011;25(3):338–43. https://doi.org/10.1016/j.niox.2011.06.003.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was performed in departments of Biophysics and Urology in Faculty of Medicine in Trakya University.

Funding

This study was not supported by any specific grant from funding.

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [NA], [AA], and [GC]. All authors approved the final manuscript. The corresponding author attests that all listed authors meet the authorship criteria and that no other authors meeting the criteria have been omitted.

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Correspondence to Arzu Ay or Nevra Alkanli.

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The authors declare that they have no conflict of interest.

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For our study, ethics committee approval was obtained with the TÜTF-BAEK 2020/240 protocol code from Trakya University Faculty of Medicine Non-Invasive Clinical Research Ethics Committee.

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Signed informed consent form was collected from each individual in the patient group with BCA and healthy control group.

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Ay, A., Alkanli, N. & Cevik, G. Determination of the Roles of Endothelial Nitric Oxide Synthase 4VNTR (4a/b), G894T, T786C Gene Variations in the Bladder Cancer Development. Ind J Clin Biochem 39, 92–100 (2024). https://doi.org/10.1007/s12291-022-01090-4

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  • DOI: https://doi.org/10.1007/s12291-022-01090-4

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