Promoter polymorphisms of DNA methyltransferase 3B and risk of hepatocellular carcinoma

Lao,Yingbin; Wu,Huazhang; Zhao,Chengchegn; Wu,Qunying; Qiao,Fengchang; Fan,Hong

doi:10.3892/br.2013.142

Promoter polymorphisms of DNA methyltransferase 3B and risk of hepatocellular carcinoma

Authors:
- Yingbin Lao
- Huazhang Wu
- Chengchegn Zhao
- Qunying Wu
- Fengchang Qiao
- Hong Fan
View Affiliations

Affiliations: Department of Medical Genetics and Developmental Biology, Medical School of Southeast University and Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Nanjing, Jiangsu 210009, P.R. China, Institute of Biotechnology, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
Published online on: July 19, 2013 https://doi.org/10.3892/br.2013.142
Pages: 771-775

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Epigenetic changes in gene expression, including DNA methylation and histone modifications, may contribute to the development of HCC. Polymorphisms of the DNA methyltransferase 3B (DNMT3B) gene may affect the activity of this enzyme and increase the susceptibility to several types of cancer, including HCC. To confirm this hypothesis, we investigated the association between single‑nucleotide polymorphisms‑149C>T (rs2424913) and ‑579G>T (rs1569686) in the promoter region of DNMT3B and the risk of HCC. DNMT single‑nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction‑restriction fragment length polymorphism in 108 HCC patients and 240 healthy controls matched for age, gender and ethnicity. The DNMT3B‑149 TT genotype was not significantly associated with an increased risk of HCC. The frequency of DNMT3B‑149C was 0.46% in HCC patients and 1.39% in healthy individuals, whereas the frequency of DNMT3B‑579G was 8.33% in HCC patients and 10.42% in healthy individuals. No significant differences were observed in the genotype or allelic distribution between HCC patients and controls. In conclusion, DNMT3B‑149C>T and ‑579G>T polymorphisms are not significantly associated with an increased risk of HCC. these results demonstrated that these particular SNPs may not be used as biomarkers to predict susceptibility to HCC.

View Figures

View References

1	Wang Z, Cao Y, Jiang C, et al: Lack of association of two common polymorphisms rs2910164 and rs11614913 with susceptibility to hepatocellular carcinoma: a meta-analysis. PLoS One. 7:e400392012. View Article : Google Scholar : PubMed/NCBI
2	Thomas MB, Jaffe D, Choti MM, et al: Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol. 28:3994–4005. 2010. View Article : Google Scholar
3	Chen CJ and Chen DS: Interaction of hepatitis B virus, chemical carcinogen, and genetic susceptibility: multistage hepatocarcinogenesis with multifactorial etiology. Hepatology. 36:1046–1049. 2002. View Article : Google Scholar
4	Kong SY, Park JW, Lee JA, et al: Association between vascular endothelial growth factor gene polymorphisms and survival in hepatocellular carcinoma patients. Hepatology. 46:446–455. 2007. View Article : Google Scholar : PubMed/NCBI
5	Deng G, Zhou G, Zhang R, et al: Regulatory polymorphisms in the promoter of CXCL10 gene and disease progression in male hepatitis B virus carriers. Gastroenterology. 134:716–726. 2008. View Article : Google Scholar : PubMed/NCBI
6	Clifford RJ, Zhang J, Meerzaman DM, et al: Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma. Hepatology. 52:2034–2043. 2010. View Article : Google Scholar : PubMed/NCBI
7	Long XD, Ma Y, Zhou YF, et al: Polymorphism in xeroderma pigmentosum complementation group C codon 939 and aflatoxin B1-related hepatocellular carcinoma in the Guangxi population. Hepatology. 52:1301–1309. 2010. View Article : Google Scholar
8	Kumar V, Kato N, Urabe Y, et al: Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nat Genet. 43:455–458. 2011. View Article : Google Scholar : PubMed/NCBI
9	Zhang H, Zhai Y, Hu Z, et al: Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers. Nat Genet. 42:755–758. 2010. View Article : Google Scholar : PubMed/NCBI
10	Figueroa ME, Lugthart S, Li Y, et al: DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell. 17:13–27. 2010. View Article : Google Scholar
11	Noushmehr H, Weisenberger DJ, Diefes K, et al: Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 17:510–522. 2010. View Article : Google Scholar : PubMed/NCBI
12	Portela A and Esteller M: Epigenetic modifications and human disease. Nat Biotechnol. 28:1057–1068. 2010. View Article : Google Scholar : PubMed/NCBI
13	Esteller M: Epigenetics in cancer. N Engl J Med. 358:1148–1159. 2008. View Article : Google Scholar
14	Shen H, Wang L, Spitz MR, et al: A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. Cancer Res. 62:4992–4995. 2002.PubMed/NCBI
15	Wang L, Rodriguez M, Kim ES, et al: A novel C/T polymorphism in the core promoter of human de novo cytosine DNA methyltransferase 3B6 is associated with prognosis in head and neck cancer. Int J Oncol. 25:993–999. 2004.PubMed/NCBI
16	Taberlay PC and Jones PA: DNA methylation and cancer. Prog Drug Res. 67:1–23. 2011.
17	Miller SA, Dykes DD and Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16:12151988. View Article : Google Scholar : PubMed/NCBI
18	Paz MF, Fraga MF, Avila S, et al: A systematic profile of DNA methylation in human cancer cell lines. Cancer Res. 63:1114–1121. 2003.PubMed/NCBI
19	Egger G, Liang G, Aparicio A, et al: Epigenetics in human disease and prospects for epigenetic therapy. Nature. 429:457–463. 2004. View Article : Google Scholar : PubMed/NCBI
20	Wjst M: Target SNP selection in complex disease association studies. BMC Bioinformatics. 5:922004. View Article : Google Scholar : PubMed/NCBI
21	Fang C, Sun W, Han H, et al: The -149C>T polymorphism of DNMT3B is not associated with colorectal cancer risk: Evidence from a meta-analysis based on case-control studies. Exp Ther Med. 4:728–732. 2012.
22	Lee SJ, Jeon HS, Jang JS, et al: DNMT3B polymorphisms and risk of primary lung cancer. Carcinogenesis. 26:403–409. 2005.PubMed/NCBI
23	Hong YS, Lee HJ, You CH, et al: DNMT3b 39179GT polymorphism and the risk of adenocarcinoma of the colon in Koreans. Biochem Genet. 45:155–163. 2007. View Article : Google Scholar : PubMed/NCBI
24	Khorshied MM and El-Ghamrawy MK: DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt. Gene. 511:34–37. 2012.
25	Zhao H, Du W, Gu D, et al: DNMT3B 579G>T promoter polymorphism and the risk for idiopathic thrombocytopenic purpura in a Chinese population. Acta Haematol. 122:31–35. 2009.
26	Chang KP, Hao SP, Liu CT, et al: 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. 2007. View Article : Google Scholar : PubMed/NCBI
27	Fan H, Liu DS, Zhang SH, et al: DNMT3B 579 G>T promoter polymorphism and risk of esophagus carcinoma in Chinese. World J Gastroenterol. 14:2230–2234. 2008.
28	Zhu S, Zhang H, Tang Y, et al: DNMT3B polymorphisms and cancer risk: a meta analysis of 24 case-control studies. Mol Biol Rep. 39:4429–4437. 2012. View Article : Google Scholar : PubMed/NCBI
29	Wu Y and Lin JS: DNA methyltransferase 3B promoter polymorphism and its susceptibility to primary hepatocellular carcinoma in the Chinese Han nationality population: a case-control study. World J Gastroenterol. 13:6082–6086. 2007. View Article : Google Scholar
30	Ezzikouri S, El Feydi AE, Benazzouz M, et al: Single nucleotide polymorphism in DNMT3B promoter and its association with hepatocellular carcinoma in a Moroccan population. Infect Genet Evol. 9:877–881. 2009. View Article : Google Scholar : PubMed/NCBI