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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2024; 70(4): 42-49


TaqI polymorphism of VDR gene in colorectal cancer and Crohn’s disease patients

M.R. Lozynska1, L.Y. Lozynska2, R.O. Pinyazhko2, I.E.Gaybonyuk3, O.R. Pinyazhko2, O.M. Fedota4

  1. SI ”Institute of Hereditary Pathology of National Academy of Medical Sciences of Ukraine”, Lviv, Ukraine
  2. Danylo Halytsky Lviv National Medical University, Ukraine
  3. SMDC “LeoGENE”, Lviv, Ukraine
  4. ”LLC ”AMS”, Kharkiv, Ukraine
DOI: https://doi.org/10.15407/fz70.04.042


Abstract

To study the relation of TaqI polymorphism of VDR gene with age, sex and the disease phenotype in patients with colorectal cancer (CRC) and Crohn’s disease (CD) from western regions of Ukraine. Fifty six patients with CRC, 46 patients with CD and 65 control individuals were included in this research. Assessment of TaqI polymorphism was performed using PCR-RFLP method. The genotype-phenotype association for this polymorphism was analyzed. The frequency of tt genotype in patients with CRC is 0.107 and among the control group is 0.138, OR (95% CI 0.248-2.246). The ratio of genotypes TT:Tt:tt in patients with CRC and in control was 37.5%:51.8%:10.7% and 44.6%:41.6%:13.8%. In men with Tt genotype the average age of CRC onset was 57.6 ± 3.6 years, in women with TT genotypethe mean age of the disease onset was 54.5 ± 4.5 years. The frequency of tt genotype in the patients with CD is 0.217 and among the control group is 0.138, OR (95% CI 0.640–4.666). The Tt genotype was detected in a half of patients with CD and TT genotype was found more frequently in control.The ratio of genotypes in men and women with CD was 38.0%:38.0%:24.0% and 20.0%:60.0%:20.0%. Among patients with CD, who underwent surgery, 33.3% individuals were carriers of tt genotype. It was confirmed no statistically significant difference in the allele frequencies and genotype distributions of Taq1 mutation in patients with CRC and CD in comparison to control group. The ratio of men and women with Tt genotype by groups of B1-B3 forms of CD behaviour according to the Montreal classification is differs, in particular, women with Tt genotype are four times more likely to have the B1 form. A study of Taq1 mutation might contribute to the identification of the groups that are at the greatest risk of severe form of CD.

Keywords: VDR gene TaqI polymorphism; genotypes distribution; colorectal cancer; Crohn`s disease; sex; age at the diseases onset; disease phenotype.

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-917. CrossRef PubMed
  2. Toiyama Y, Okugawa Y, Goel A. DNA methylation and microRNA biomarkers for noninvasive detection of gastric and colorectal cancer. Biochem Biophys Res Commun. 2014;455:43-57. CrossRef PubMed PubMedCentral
  3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA , Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2018; 68:394-424. CrossRef PubMed
  4. Bulletin of the National Cancer Registry of Ukraine, Vol. 24 Kyiv . 2023.
  5. Pan Z, Chen M, Hu X, Wang H, Yang J, Zhang C, F Pan, Sun G. Associations between VDR gene polymorphisms and colorectal cancer susceptibility: an updated metaanalysis based on 39 case-control studies. Oncotarget. 2018 Feb 27; 9(16):13068-76. CrossRef PubMed PubMedCentral
  6. Laczmanska I, Laczmanski L, Bebenek M, Karpinski P, Czemarmazowicz H, Ramsey D, Milewicz A, Sasiadek MM. Vitamin D population. Tumour Biol. 2014;35:12397-401. CrossRef PubMed PubMedCentral
  7. Latacz M, Rozmus D, Fiedorowicz E, Snarska J, Jarmołowska B, Kordulewska N, Savelkoul H, Cieślińska A. Vitamin D receptor (VDR) gene polymorphism in patients diagnosed with colorectal cancer. Nutrients. 2021 Jan; 13(1): 200. CrossRef PubMed PubMedCentral
  8. Gandini S, Gnagnarella P, Serrano D, Pasquali E, Raimondi S. Vitamin D receptor polymorphisms and cancer. Adv Exp Med Biol. 2014:810:69-105. CrossRef PubMed
  9. Chubb D, Broderick P, Frampton M, Kinnersley B , Sherborne A , Penegar S, Lloyd A , Ma YP, Dobbins SE, Houlston RS. Genetic diagnosis of high-penetrance susceptibility for colorectal cancer (CRC) is achievable for a high proportion of familial CRC by exome sequencing. J Clin Oncol. 2015;33:426-32. CrossRef PubMed
  10. Gausman V, Dornblaser D, Anand S, Hayes RB , O'Connell K, Du M , Liang PS. Risk factors associated with early-onset colorectal cancer. Clin Gastroenterol Hepatol. 2020;18:2752-9. CrossRef PubMed PubMedCentral
  11. Di Rosa M, Malaguarnera M, Zanghì A, Passaniti A, Malaguarnera L. Vitamin D3 insufficiency and colorectal cancer. Crit Rev Oncol Hematol. 2013;88:594-612. CrossRef PubMed
  12. Ferrer-Mayorga G, Larriba MJ, Crespo P, Muñoz А. Mechanisms of action of vitamin D in colon cancer. J Steroid Biochem Mol Biol. 2019;185:1-6. CrossRef PubMed
  13. Yang M, Ji W, Xu N, Zong C, Gu J, Guo X, Zhang L. Association between vitamine D receptor polymorphisms with colorectal cancer susceptibility: a systemic metaanalysis. Medicine. 2023. 102(1): e32575. CrossRef PubMed PubMedCentral
  14. Al-Ghafari AB, Balamash KS, Al Doghaither HA. TaqI and ApaI Variants of vitamin D receptor gene increase the risk of colorectal cancer in a Saudi population. Saudi J Med Med Sci. 2020;8:188-95. CrossRef PubMed PubMedCentral
  15. Slatter MY, Hoffman M, Neuhausen S. Variants of the VDR gene and risk of colon cancer (United States). Cancer Causes Control. 2001 May;12(4):12:359-64. CrossRef PubMed
  16. Murtaugh MS, Ma KN, Potter JD, Caan BJ, Wolff RK, Slattery ML. Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance, and colon and rectal cancer. Nutr Cancer. 2006;55:35-43. CrossRef PubMed
  17. Al-Ghafari AB, Balamash KS, Al Doghaither HA. Relationship between serum vitamin d and calcium levels and vitamin D receptor gene polymorphisms in colorectal cancer. Biomed Res Int. 2019:18571541-7. CrossRef PubMed PubMedCentral
  18. Rubin DT, Huo D, Kinnucan JA, Sedrak MS, McCullom NE, et al. Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study. Clin Gastroenterol Hepatol. 2013 Dec;11(12):1601-8.e1-4. CrossRef PubMed PubMedCentral
  19. Lopes BV, Ribeiro VL, Marques LOR, Santos LE, LeãoCordeiro, Bernardes JA, Cordeiro SAT. Polymorphisms of the Vitamin D receptor gene in Crohn's disease . Coloproctology. (Rio J.) 41 (02) • Apr-Jun 2021 •. CrossRef
  20. Luo YY, Shu XL, Zhao H, Yu JD, Ma M, Chen J. Association between vitamin D receptor gene polymorphisms and pediatric Crohn's disease in China: A study based on gene sequencing. Chin J Contemporary Pediatr 2013;15(11):1006-8.
  21. Xue LN, Xu KQ, Zhang W, Wang Q, Wu J, Wang XY. Associations between vitamin D receptor polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis. Inflamm Bowel Dis 2013;19(01):54-60. CrossRef PubMed
  22. Leskovar D, Meštrović T, Barešić A, Kraljević I, Panek M. The Role of Vitamin D in inflammatory Bowel disease - assessing therapeutic and preventive potential of supplementation and food fortification. Food Technol Biotechnol. 2018; 56(4): 455-63. CrossRef PubMed PubMedCentral
  23. Noble L, McCullough J, Ho W, Lees CW, Nimmo E, Drummond H, Bear S, Hannan J, Millar C, Ralston SH, Satsangi J. Low body mass not vitamin D receptor polymorphisms predict osteoporosis in patients with inflammatory bowel disease. Aliment Pharmacol Therap. 2008;27(7):588-96. CrossRef PubMed
  24. Louis E, Michel V, Hugot JP, Reenaers C, Fontaine F, Delforge, F ElYafi M, Colombel JF, Belaiche J. Early development of stricturing or penetrating pattern in Crohn's disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype. Gut. 2003 Apr; 52(4): 552-7. CrossRef PubMed PubMedCentral
  25. Lopes EW, Lochhead P, Burke KE, Richter JM, Ananthakrishnan AN., Chan AT, Khalili H. Risk factors for incident inflammatory Bowel disease according to disease phenotype. Clin Gastroenterol Hepatol. 2022 Oct; 20(10): 2347-57.e14. CrossRef PubMed PubMedCentral
  26. Martin K, Radlmayr M, Borchers R, Heinzlmann M, Folwaczny C. Candidate genes lolocalized to linkage regions in inflammatory bowel disease. Digestion. 2002;66(2):121-6. CrossRef PubMed

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