Association study of the polymorphisms rs2228611 of the DNMT1 gene and rs1569686 of the DNMT3B gene with bladder cancer development in a sample of the Algerian population

Document Type : Original article

Authors

1 Université Des Sciences Et de La Technologie d’Oran Mohamed-Boudiaf USTOMB El Mnaouar, BP 1505, Bir El Djir, 31000 Oran, Algerie. Laboratoire Génétique Moléculaire Et Cellulaire (LGMC) USTOMB

2 Etablissement Hospitalier Universitaire d'Oran EHU 1 Novembre 1954, service Chirurgie Urologique, Oran, Algerie

Abstract

Bladder cancer (BC) is a multifactorial disease with a poorly understood main cause. In this study, we aimed to evaluate the effect of the polymorphisms rs2228611 of the DNMT1 gene and rs1569686 of the DNMT3B gene on the susceptibility to develop Bladder Cancer in the Algerian population. A case-control study design was adopted, with DNA samples of 114 BC patients and 123 healthy controls. We found that the rs2228611 of the DNMT1 gene was strongly associated with an increased risk of BC development under genetic models: Codominant AG vs. GG (OR=2.54, 95% CI=1.21-5.51, adj p=0.015) and dominant AA+AG vs. GG (OR=2.24, 95% CI=1.12-4.60, adj p=0.023). However, no statistically significant association was observed between the rs1569686 of the DNMT3B gene and the predisposition to BC. To the best of our knowledge, this is the first peer-reviewed study to evaluate the effect of the rs2228611 polymorphism on bladder cancer occurrence. Our results suggest that the rs2228611 might be a potential biomarker for BC development risk. Additional studies are needed to validate our findings.

Keywords


  1. Jubber I, Ong S, Bukavina L, Black PC, Compérat E, Kamat AM, Kiemeney L, Lawrentschuk N, Lerner SP, Meeks JJ, Moch H, Necchi A, Panebianco V, Sridhar SS, Znaor A, Catto JWF, Cumberbatch MG. Epidemiology of bladder cancer in 2023: A systematic review of risk factors. Eur Urol 2023;84:176-190.
  2. Halaseh SA, Halaseh S, Alali Y, Ashour ME, Alharayzah MJ. A Review of the Etiology and Epidemiology of Bladder Cancer: All You Need To Know. Cureus 2022;14:e27330.
  3. Fraumeni Jr JF, Thomas LB. Malignant bladder tumors in a man and his three sons. JAMA 1967;201:507-509.
  4. Zhang X, Zhang Y. Bladder cancer and genetic mutations. Cell Biochem Biophys 2015; 73:65-69.
  5. Dupont C, Armant DR, Brenner CA. Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med 2009;27:351-357.
  6. Hentschel AE, Beijert IJ, Bosschieter J, Kauer PC, Vis AN, Lissenberg-Witte BI, van Moorselaar RJA, Steenbergen RDM, Nieuwenhuijzen JA. Bladder cancer detection in urine using DNA methylation markers: a technical and prospective preclinical validation. Clin Epigenetics 2022;14:19.
  7. Murphy TM, Mullins N, Ryan M, Foster T, Kelly C, McClelland R, O’Grady J, Corcoran E, Brady J, Reilly M, Jeffers A, Brown K, Maher A, Bannan N, Casement A, Lynch D, Bolger S, Buckley A, Quinlivan L, Daly L, Kelleher C, Malone KM. Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients. Genes Brain Behav 2013;12:125-132.
  8. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
  9. Khatami F, Noorinayer B, Ghiasi S, Mohebi R, Hashemi M, Zali MR. Lack of effects of single nucleotide polymorphisms of the DNA methyltransferase 1 gene on gastric cancer in Iranian patients: a case control study. Asian Pac J Cancer Prev 2009;10:1177-1182.
  10. Coppedè F, Ricciardi R, Denaro M, Rosa AD, Provenzano C, Bartoccioni E, Baggiani A, Lucchi M, Mussi A, Migliore L. Association of the DNMT3B -579G>T polymorphism with risk of thymomas in patients with myasthenia gravis. PLos One 2013;8:e80846.
  11. Chung CJ, Chang CH, Liu CS, Huang CP, Chang YH, Chien SN, Tsai PH, Hsieh HA. Association of DNA methyltransferases 3A and 3B polymorphisms, and plasma folate levels with the risk of urothelial carcinoma. PLoS One 2014;9:e104968.
  12. Touala-Chaila Z, Abderrahmane RK, Benseddik K, Meroufel DN. A meta-analysis on the susceptibility to the development of bladder cancer in the presence of DNMT3A, DNMT3B, and MTHFR gene polymorphisms. Afr J Urol 2022;28:32.
  13. Chang KP, Hao SP, Tsang NM, Chang YL, Cheng MH, Liu CT, Lee YS, Tsai CL, Lee TJ, Wang TH, Tsai CN. Gene expression and promoter polymorphisms of DNA methyltransferase 3B in nasopharyngeal carcinomas in Taiwanese people: a case-control study. Oncol Rep 2008;19:217-222.
  14. Zhang Y, Xu H, Shen Y, Gong Z, Xiao T. Association of DNMT3B -283 T>C and -579 G>T polymorphisms with decreased cancer risk: evidence from a meta-analysis. Int J Clin Exp Med 2015;8:13028-13038.
  15. Bayramov B, Bayramov N, Aslanov H, Abbasov M, Mammadova S, Eynullazada K, Gahramanova F, Yagublu V. Investigation of the DNMT3B–579 G>T promoter polymorphism in patients with colorectal cancer in an Azerbaijani population. Asian Pac J Cancer Prev 2022;23:1879-1884.
  16. Li H, Li W, Liu S, Zong S, Wang W, Ren J, Li Q, Hou F, Shi Q. DNMT1, DNMT3A and DNMT3B polymorphisms associated with gastric cancer risk: A systematic review and meta-analysis. EBioMedicine 2016;13:125-131.
  17. Chung CH, Chang CH, Liu CS, Chang YH, Chung MC. The effect of cigarette smoking and DNA methyltransferase genes polymorphisms on urothelial carcinoma risk in Taiwan. Environment and Health—Bridging South, North, East and West: Conference of ISEE, ISES and ISIAQ 2013. https://doi.org/10.1289/isee.2013.P-3-11-2
  18. Li H, Liu Jw, Sun LP, Yuan Y. A meta-analysis of the association between DNMT1 polymorphisms and cancer risk. Biomed Res Int 2017;2017:3971259.
  19. Mostowska A, Sajdak S, Pawlik P, Lianeri M, Jagodzinski PP. DNMT1, DNMT3A and DNMT3B gene variants in relation to ovarian cancer risk in the Polish population. Mol Biol Rep 2013; 40:4893-4899.
  20. Zhang W, Xu J. DNA methyltransferases and their roles in tumorigenesis. Biomarker Res 2017;5:1.
  21. Veland N, Chen T. Chapter 2-Mechanisms of DNA Methylation and Demethylation During Mammalian Development. In: Tollefsbol TO, editor. Handbook of Epigenetics (Second Edition). Academic Press 2017. p. 11–24.
  22. Jia Z, Wu X, Cao D, Wang C, You L, Jin M, Wen S, Cao X, Jiang J. Polymorphisms of the DNA methyltransferase 1 gene predict survival of gastric cancer patients receiving tumorectomy. Dis Markers 2016;2016:8578064.
  23. Saradalekshmi KR, Neetha NV, Sathyan S, Nair IV, Nair CM, Banerjee M. DNA methyl transferase (DNMT) gene polymorphisms could be a primary event in epigenetic susceptibility to schizophrenia. PLoS One 2014;9:e98182.
  24. Cheng P, Chen H, Zhang RP, Liu S, Zhou-Cun A. Polymorphism in DNMT1 may modify the susceptibility to oligospermia. Reprod Biomed Online 2014;28:644-649.
  25. Presnyak V, Alhusaini N, Chen YH, Martin S, Morris N, Kline N, Olson S, Weinberg D, Baker KE, Graveley BR, Coller J. Codon optimality is a major determinant of mRNA stability. Cell 2015;160:1111-1124.
  26. Corbin JM, Ruiz-Echevarría MJ. One-carbon metabolism in prostate cancer: The role of androgen signaling. Int J Mol Sci 2016;17:1208.
  27. Cao S, Zhu X, Zhang C, Qian H, Schuttler HB, Gong J, Xu Y. Competition between DNA methylation, nucleotide synthesis and anti-oxidation in cancer versus normal tissues. Cancer Res 2017;77:4185-4195.