Brief Article
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World J Hepatol. May 27, 2012; 4(5): 169-175
Published online May 27, 2012. doi: 10.4254/wjh.v4.i5.169
Global hypomethylation in hepatocellular carcinoma and its relationship to aflatoxin B1 exposure
Yu-Jing Zhang, Hui-Chen Wu, Hulya Yazici, Ming-Whei Yu, Po-Huang Lee, Regina M Santella
Yu-Jing Zhang, Hui-Chen Wu, Regina M Santella, Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, 630 W 168Th St., New York, NY 10032, United States
Hulya Yazici, Department of Oncology, Oncology Institute, Istanbul University, Istanbul 34093, Turkey
Ming-Whei Yu, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei 10002, Taiwan, China
Po-Huang Lee, Department of Surgery, College of Medicine, National Taiwan University, Taipei 10002, Taiwan, China
Author contributions: Zhang YJ and Santella RM designed the research; Zhang YJ and Yazici H performed the assays; Wu HC did the statistical analysis; Yu MW and Lee PH supplied paired hepatocellular carcinoma samples and clinical data; and Zhang YJ and Santella RM wrote the paper.
Supported by A grant from the National Institute of Health, No. ES005116 and No. P30ES009089
Correspondence to: Yu-Jing Zhang, MD, Senior Research Scientist, Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, 630 W 168Th St., New York, NY 10032, United States. yz6@columbia.edu
Telephone: +1-212-3058158 Fax: +1-212-3055328
Received: November 19, 2011
Revised: February 2, 2012
Accepted: April 27, 2012
Published online: May 27, 2012
Abstract

AIM: To determine global DNA methylation in paired hepatocellular carcinoma (HCC) samples using several different assays and explore the correlations between hypomethylation and clinical parameters and biomarkers, including that of aflatoxin B1 exposure.

METHODS: Using the radio labeled methyl acceptance assay as a measure of global hypomethylation, as well as two repetitive elements, including satellite 2 (Sat2) by MethyLight and long interspersed nucleotide elements (LINE1), by pyrosequencing.

RESULTS: By all three assays, mean methylation levels in tumor tissues were significantly lower than that in adjacent tissues. Methyl acceptance assay log (mean ± SD) disintegrations/min/ng DNA are 70.0 ± 54.8 and 32.4 ± 15.6, respectively, P = 0.040; percent methylation of Sat2 42.2 ± 55.1 and 117.9 ± 88.8, respectively, P < 0.0001 and percent methylation LINE1 48.6 ± 14.8 and 71.7 ± 1.4, respectively, P < 0.0001. Aflatoxin B1-albumin (AFB1-Alb) adducts, a measure of exposure to this dietary carcinogen, were inversely correlated with LINE1 methylation (r = -0.36, P = 0.034).

CONCLUSION: Consistent hypomethylation in tumor compared to adjacent tissue was found by the three different methods. AFB1 exposure is associated with DNA global hypomethylation, suggesting that chemical carcinogens may influence epigenetic changes in humans.

Keywords: Hepatocellular carcinoma; Epigenetics; Hypomethylation; [3H]-methyl acceptance assay; Satellite 2; Long interspersed nucleotide element-1; Aflatoxin B1