Skip to main content
SpringerLink
Log in

Association of the DNMT3B polymorphism with colorectal adenomatous polyps and adenocarcinoma

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

DNMT3B is an important enzyme to modulate the methylation status in mammalian cells. The aim of this study is to investigate the correlation of the DNMT3B G39179T polymorphism with the susceptibilities of colorectal adenomatous polyps and adenocarcinoma. This case-control study included 146 colorectal adenomatous polyps, 170 colorectal adenocarcinoma patients, and 157 normal controls. DNMT3B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Family history of colorectal cancer significantly increases the risk of developing colorectal adenomatous polyps and adenocarcinoma. The genotype frequency of DNMT3B polymorphism (T/T and G/T + G/G) in adenocarcinoma patients was significantly different from that in controls (P value = 0.01). Compared with DNMT3B T/T genotype, the G allelotype (G/T + G/G genotype) had lower risk to develop colorectal adenocarcinoma (OR = 0.50, 95% CI = 0.29–0.87); while there was no significant difference between the colorectal adenomatous polyps patients and controls (OR = 0.63, 95% CI = 0.37–1.09), although descending tendency could be found in this polyps group. In the stratification analysis, a significant association was confined to subgroups of age < 55 (OR = 0.31, 95% CI = 0.12–0.84) and males (OR = 0.35, 95% CI = 0.17–0.71). Meanwhile, combined G/T + G/G genotypes were found to have a lower risk in non-drinkers to develop both colorectal adenomatous polyps and adenocarcinoma (OR = 0.54, 95% CI = 0.31–0.96 and OR = 0.48, 95% CI = 0.27–0.84, respectively). This study also showed a distinct difference in the distribution of DNMT3B G39179T SNP in different ethnics. DNMT3B G39179T SNP may be a potential genetic susceptibility factor for adenocarcinoma of the colon, especially in younger Chinese Han non-drinker men.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Lee JJ, Chu E (2007) Update on clinical data combining capecitabine with targeted agents in newly diagnosed colorectal cancer. Clin Colorectal Cancer 7(Suppl 1):S16–S20

    Article  CAS  PubMed  Google Scholar 

  2. Morson BC (1978) Symposium on colorectal cancer. 1. Pathology of colorectal cancer. Can J Surg 21:206–208

    CAS  PubMed  Google Scholar 

  3. Giovannucci E, Rimm EB, Ascherio A et al (1995) Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst 87:265–273

    Article  CAS  PubMed  Google Scholar 

  4. Linhart HG, Lin H, Yamada Y et al (2007) Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes Dev 21:3110–3122

    Article  CAS  PubMed  Google Scholar 

  5. Jones PA, Laird PW (1999) Cancer epigenetics comes of age. Nat Genet 21:163–167

    Article  CAS  PubMed  Google Scholar 

  6. Baylin SB, Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16:168–174

    Article  CAS  PubMed  Google Scholar 

  7. Bestor T, Laudano A, Mattaliano R, Ingram V (1988) Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol 203:971–983

    Article  CAS  PubMed  Google Scholar 

  8. Okano M, Xie S, Li E (1998) Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19:219–220

    Article  CAS  PubMed  Google Scholar 

  9. Rhee I, Bachman KE, Park BH et al (2002) DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 416:552–556

    Article  CAS  PubMed  Google Scholar 

  10. Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (2002) Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases. EMBO J 21:4183–4195

    Article  CAS  PubMed  Google Scholar 

  11. Bestor TH (1992) Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain. EMBO J 11:2611–2617

    CAS  PubMed  Google Scholar 

  12. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257

    Article  CAS  PubMed  Google Scholar 

  13. Robertson KD, Uzvolgyi E, Liang G et al (1999) The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res 27:2291–2298

    Article  CAS  PubMed  Google Scholar 

  14. Shen H, Wang L, Spitz MR et al (2002) A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. Cancer Res 62:4992–4995

    CAS  PubMed  Google Scholar 

  15. Montgomery KG, Liu MC, Eccles DM, Campbell IG (2004) The DNMT3B C → T promoter polymorphism and risk of breast cancer in a British population: a case-control study. Breast Cancer Res 6:R390–R394

    Article  CAS  PubMed  Google Scholar 

  16. Hong YS, Lee HJ, You CH et al (2007) DNMT3b 39179GT polymorphism and the risk of adenocarcinoma of the colon in Koreans. Biochem Genet 45:155–163

    Article  CAS  PubMed  Google Scholar 

  17. Singal R, Das PM, Manoharan M, Reis IM, Schlesselman JJ (2005) Polymorphisms in the DNA methyltransferase 3b gene and prostate cancer risk. Oncol Rep 14:569–573

    CAS  PubMed  Google Scholar 

  18. Liu Z, Wang L, Wang LE, Sturgis EM, Wei Q (2008) Polymorphisms of the DNMT3B gene and risk of squamous cell carcinoma of the head and neck: a case-control study. Cancer Lett 268:158–165

    Article  CAS  PubMed  Google Scholar 

  19. Fan H, Zhang F, Hu J, Liu D, Zhao Z (2008) Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study. J Exp Clin Cancer Res 27:24

    Article  PubMed  Google Scholar 

  20. Goll MG, Bestor TH (2005) Eukaryotic cytosine methyltransferases. Annu Rev Biochem 74:481–514

    Article  CAS  PubMed  Google Scholar 

  21. Schmidt WM, Sedivy R, Forstner B et al (2007) Progressive up-regulation of genes encoding DNA methyltransferases in the colorectal adenoma-carcinoma sequence. Mol Carcinog 46:766–772

    Article  CAS  PubMed  Google Scholar 

  22. Kim H, Kwon YM, Kim JS et al (2006) Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancer. Cancer 107:1042–1049

    Article  CAS  PubMed  Google Scholar 

  23. Chen CL, Yan X, Gao YN, Liao QP (2005) Expression of DNA methyltransferase 1, 3A and 3B mRNA in the epithelial ovarian carcinoma. Zhonghua Fu Chan Ke Za Zhi 40:770–774

    PubMed  Google Scholar 

  24. Yakushiji T, Uzawa K, Shibahara T, Noma H, Tanzawa H (2003) Over-expression of DNA methyltransferases and CDKN2A gene methylation status in squamous cell carcinoma of the oral cavity. Int J Oncol 22:1201–1207

    CAS  PubMed  Google Scholar 

  25. Saito Y, Kanai Y, Nakagawa T et al (2003) Increased protein expression of DNA methyltransferase (DNMT) 1 is significantly correlated with the malignant potential and poor prognosis of human hepatocellular carcinomas. Int J Cancer 105:527–532

    Article  CAS  PubMed  Google Scholar 

  26. Buckland PR (2006) The importance and identification of regulatory polymorphisms and their mechanisms of action. Biochim Biophys Acta 1762:17–28

    CAS  PubMed  Google Scholar 

  27. Lee SJ, Jeon HS, Jang JS et al (2005) DNMT3B polymorphisms and risk of primary lung cancer. Carcinogenesis 26:403–409

    Article  CAS  PubMed  Google Scholar 

  28. Fan H, Liu DS, Zhang SH et al (2008) DNMT3B 579 G > T promoter polymorphism and risk of esophagus carcinoma in Chinese. World J Gastroenterol 14:2230–2234

    Article  CAS  PubMed  Google Scholar 

  29. Chang KP, Hao SP, Liu CT et al (2007) Promoter polymorphisms of DNMT3B and the risk of head and neck squamous cell carcinoma in Taiwan: a case-control study. Oral Oncol 43:345–351

    Article  CAS  PubMed  Google Scholar 

  30. Lee GY, Jang JS, Lee SY et al (2005) XPC polymorphisms and lung cancer risk. Int J Cancer 115:807–813

    Article  CAS  PubMed  Google Scholar 

  31. Neugut AI, Jacobson JS, De Vivo I (1993) Epidemiology of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev 2:159–176

    CAS  PubMed  Google Scholar 

  32. Fahy B, Bold RJ (1998) Epidemiology and molecular genetics of colorectal cancer. Surg Oncol 7:115–123

    Article  CAS  PubMed  Google Scholar 

  33. Cappell MS (2008) Pathophysiology, clinical presentation, and management of colon cancer. Gastroenterol Clin North Am 37:1–24 v

    Article  PubMed  Google Scholar 

  34. Ryan BM, Weir DG (2001) Relevance of folate metabolism in the pathogenesis of colorectal cancer. J Lab Clin Med 138:164–176

    Article  CAS  PubMed  Google Scholar 

  35. Mizoue T, Inoue M, Wakai K et al (2008) Alcohol drinking and colorectal cancer in Japanese: a pooled analysis of results from five cohort studies. Am J Epidemiol 167:1397–1406

    Article  PubMed  Google Scholar 

  36. Homann N, Tillonen J, Salaspuro M (2000) Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency. Int J Cancer 86:169–173

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endoscopy, The 4th Affiliated Hospital, Hebei Medical University, 12 Jiankang Road, 050011, Shijiazhuang, Hebei, People’s Republic of China

    Xiaoqing Guo, Liwei Zhang, Mingli Wu, Limian Er, Shunping Wang, Yang Gao, Weifang Yu, Zhibin Xu & Shijie Wang

  2. Department of Molecular Biology, Hebei Tumor Institute, 050011, Shijiazhuang, Hebei, People’s Republic of China

    Na Wang

  3. Department of Gastroenterology, Tangshan People’s Hospital, 063000, Tangshan, Hebei, People’s Republic of China

    Yanfeng Liu

  4. Department of Gastroenterology, Shijiazhuang Central Hospital, 050011, Shijiazhuang, Hebei, People’s Republic of China

    Hui Xue

Authors
  1. Xiaoqing Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liwei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mingli Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Na Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanfeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Limian Er
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shunping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Weifang Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hui Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhibin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shijie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shijie Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guo, X., Zhang, L., Wu, M. et al. Association of the DNMT3B polymorphism with colorectal adenomatous polyps and adenocarcinoma. Mol Biol Rep 37, 219–225 (2010). https://doi.org/10.1007/s11033-009-9626-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-009-9626-z

Keywords

Search

Navigation