TDG Gene Polymorphisms and Their Possible Association with Colorectal Cancer: A Case Control Study

Overview

Journal J Oncol

Specialty Oncology

Date 2019 Jun 27

PMID 31239841

Citations 7

Authors

Narasimha Reddy Parine

Ibrahim O Alanazi

Jilani Purusottapatnam Shaik

Sooad Aldhaian

Abdulrahman M Aljebreen

Othman Alharbi

Majid A Almadi

Nahla A Azzam

Mohammad Alanazi

Affiliations

Soon will be listed here.

Abstract

Genetic alterations that might lead to colorectal cancer involve essential genes including those involved in DNA repair, inclusive of base excision repair (BER). () is one of the most well characterized BER genes that catalyzes the removal of thymine moieties from G/T mismatches and is also involved in many cellular functions, such as the regulation of gene expression, transcriptional coactivation, and the control of epigenetic DNA modification. Mutation of the gene is implicated in carcinogenesis. In the present study, we aimed to investigate the association between gene polymorphisms and their involvement in colon cancer susceptibility. One hundred blood samples were obtained from colorectal cancer patients and healthy controls for the genotyping of seven SNPs in the gene. DNA was extracted from the blood, and the polymorphic sites (SNPs) rs4135113, rs4135050, rs4135066, rs3751209, rs1866074, and rs1882018 were investigated using TaqMan genotyping. One of the six SNPs was associated with an increased risk of colon cancer. The AA genotype of the SNP rs4135113 increased the risk of colon cancer development by more than 3.6-fold, whereas the minor allele A increased the risk by 1.6-fold. It also showed a 5-fold higher risk in patients over the age of 57. SNP rs1866074 showed a significant protective association in CRC patients. The GA genotype of rs3751209 was associated with a decreased risk in males. There is a significant relationship between gene function and colorectal cancer progression.

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References

Yatsuoka T, Furukawa T, Abe T, Yokoyama T, Sunamura M, Kobari M . Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma. Int J Pancreatol. 1999; 25(2):97-102. DOI: 10.1385/IJGC:25:2:97. View

Aravind L, Koonin E . The alpha/beta fold uracil DNA glycosylases: a common origin with diverse fates. Genome Biol. 2001; 1(4):RESEARCH0007. PMC: 15025. DOI: 10.1186/gb-2000-1-4-research0007. View

Krzesniak M, Butkiewicz D, Samojedny A, Chorazy M, Rusin M . Polymorphisms in TDG and MGMT genes - epidemiological and functional study in lung cancer patients from Poland. Ann Hum Genet. 2004; 68(Pt 4):300-12. DOI: 10.1046/j.1529-8817.2004.00079.x. View

Broderick P, Bagratuni T, Vijayakrishnan J, Lubbe S, Chandler I, Houlston R . Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition. BMC Cancer. 2006; 6:243. PMC: 1624846. DOI: 10.1186/1471-2407-6-243. View

Cortazar D, Kunz C, Saito Y, Steinacher R, Schar P . The enigmatic thymine DNA glycosylase. DNA Repair (Amst). 2006; 6(4):489-504. DOI: 10.1016/j.dnarep.2006.10.013. View

Peng B, Hurt E, Hodge D, Thomas S, Farrar W . DNA hypermethylation and partial gene silencing of human thymine- DNA glycosylase in multiple myeloma cell lines. Epigenetics. 2007; 1(3):138-45. DOI: 10.4161/epi.1.3.2938. View

Metivier R, Gallais R, Tiffoche C, Le Peron C, Jurkowska R, Carmouche R . Cyclical DNA methylation of a transcriptionally active promoter. Nature. 2008; 452(7183):45-50. DOI: 10.1038/nature06544. View

Kim E, Um S . Thymine-DNA glycosylase interacts with and functions as a coactivator of p53 family proteins. Biochem Biophys Res Commun. 2008; 377(3):838-42. DOI: 10.1016/j.bbrc.2008.10.058. View

Chanson A, Parnell L, Ciappio E, Liu Z, Crott J, Tucker K . Polymorphisms in uracil-processing genes, but not one-carbon nutrients, are associated with altered DNA uracil concentrations in an urban Puerto Rican population. Am J Clin Nutr. 2009; 89(6):1927-36. PMC: 2683003. DOI: 10.3945/ajcn.2009.27429. View

10.

Penny D, Hoeppner M, Poole A, Jeffares D . An overview of the introns-first theory. J Mol Evol. 2009; 69(5):527-40. DOI: 10.1007/s00239-009-9279-5. View

11.

Curtin K, Ulrich C, Samowitz W, Wolff R, Duggan D, Makar K . Candidate pathway polymorphisms in one-carbon metabolism and risk of rectal tumor mutations. Int J Mol Epidemiol Genet. 2011; 2(1):1-8. PMC: 3077233. View

12.

Barry K, Koutros S, Berndt S, Andreotti G, Hoppin J, Sandler D . Genetic variation in base excision repair pathway genes, pesticide exposure, and prostate cancer risk. Environ Health Perspect. 2011; 119(12):1726-32. PMC: 3261977. DOI: 10.1289/ehp.1103454. View

13.

Ruczinski I, Jorgensen T, Shugart Y, Berthier Schaad Y, Kessing B, Hoffman-Bolton J . A population-based study of DNA repair gene variants in relation to non-melanoma skin cancer as a marker of a cancer-prone phenotype. Carcinogenesis. 2012; 33(9):1692-8. PMC: 3514896. DOI: 10.1093/carcin/bgs170. View

14.

Vasovcak P, Krepelova A, Menigatti M, Puchmajerova A, Skapa P, Augustinakova A . Unique mutational profile associated with a loss of TDG expression in the rectal cancer of a patient with a constitutional PMS2 deficiency. DNA Repair (Amst). 2012; 11(7):616-23. PMC: 3387372. DOI: 10.1016/j.dnarep.2012.04.004. View

15.

Wei H, Kamat A, Chen M, Ke H, Chang D, Yin J . Association of polymorphisms in oxidative stress genes with clinical outcomes for bladder cancer treated with Bacillus Calmette-Guérin. PLoS One. 2012; 7(6):e38533. PMC: 3373532. DOI: 10.1371/journal.pone.0038533. View

16.

Dalton S, Bellacosa A . DNA demethylation by TDG. Epigenomics. 2012; 4(4):459-67. PMC: 3600859. DOI: 10.2217/epi.12.36. View

17.

Meireles Da Costa N, Hautefeuille A, Cros M, Melendez M, Waters T, Swann P . Transcriptional regulation of thymine DNA glycosylase (TDG) by the tumor suppressor protein p53. Cell Cycle. 2012; 11(24):4570-8. PMC: 3562302. DOI: 10.4161/cc.22843. View

18.

Li W, Hu N, Hyland P, Gao Y, Wang Z, Yu K . Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population. Carcinogenesis. 2013; 34(7):1536-42. PMC: 3697889. DOI: 10.1093/carcin/bgt094. View

19.

Kohli R, Zhang Y . TET enzymes, TDG and the dynamics of DNA demethylation. Nature. 2013; 502(7472):472-9. PMC: 4046508. DOI: 10.1038/nature12750. View

20.

Xu X, Yu T, Shi J, Chen X, Zhang W, Lin T . Thymine DNA glycosylase is a positive regulator of Wnt signaling in colorectal cancer. J Biol Chem. 2014; 289(13):8881-90. PMC: 3979391. DOI: 10.1074/jbc.M113.538835. View