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CLC number: R735.7

On-line Access: 2011-10-08

Received: 2010-12-05

Revision Accepted: 2011-07-27

Crosschecked: 2011-09-12

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Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.10 P.805-811


Association of hypomethylation of LINE-1 repetitive element in blood leukocyte DNA with an increased risk of hepatocellular carcinoma

Author(s):  Jian-zhong Di, Xiao-dong Han, Wen-ye Gu, Yu Wang, Qi Zheng, Pin Zhang, Hui-min Wu, Zhong-zheng Zhu

Affiliation(s):  Department of General Surgery, the Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China, Department of Gastroenterology, Shanghai Guanghua Hospital, Shanghai 200052, China, Department of General Surgery, Tongji Hospital, Tongji University, Shanghai 200065, China, Department of Oncology, No. 113 Hospital of People’s Liberation Army, Ningbo 315040, China

Corresponding email(s):   zhangpindjz@163.com

Key Words:  Cancer risk, Epigenetics, Global hypomethylation, Hepatocellular carcinoma, LINE-1 repetitive element

Jian-zhong Di, Xiao-dong Han, Wen-ye Gu, Yu Wang, Qi Zheng, Pin Zhang, Hui-min Wu, Zhong-zheng Zhu. Association of hypomethylation of LINE-1 repetitive element in blood leukocyte DNA with an increased risk of hepatocellular carcinoma[J]. Journal of Zhejiang University Science B, 2011, 12(10): 805-811.

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author="Jian-zhong Di, Xiao-dong Han, Wen-ye Gu, Yu Wang, Qi Zheng, Pin Zhang, Hui-min Wu, Zhong-zheng Zhu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%T Association of hypomethylation of LINE-1 repetitive element in blood leukocyte DNA with an increased risk of hepatocellular carcinoma
%A Jian-zhong Di
%A Xiao-dong Han
%A Wen-ye Gu
%A Yu Wang
%A Qi Zheng
%A Pin Zhang
%A Hui-min Wu
%A Zhong-zheng Zhu
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 10
%P 805-811
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1000422

T1 - Association of hypomethylation of LINE-1 repetitive element in blood leukocyte DNA with an increased risk of hepatocellular carcinoma
A1 - Jian-zhong Di
A1 - Xiao-dong Han
A1 - Wen-ye Gu
A1 - Yu Wang
A1 - Qi Zheng
A1 - Pin Zhang
A1 - Hui-min Wu
A1 - Zhong-zheng Zhu
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 10
SP - 805
EP - 811
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1000422

Global DNA hypomethylation has been associated with increased risk for cancers of the colorectum, bladder, breast, head and neck, and testicular germ cells. The aim of this study was to examine whether global hypomethylation in blood leukocyte DNA is associated with the risk of hepatocellular carcinoma (HCC). A total of 315 HCC cases and 356 age-, sex- and HBsAg status-matched controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing long interspersed element-1 (LINE-1) repeats using bisulfite-polymerase chain reaction (PCR) and pyrosequencing. We observed that the median methylation level in HCC cases (percentage of 5-methylcytosine (5mC)=77.7%) was significantly lower than that in controls (79.5% 5mC) (P=0.004, Wilcoxon rank-sum test). The odds ratios (ORs) of HCC for individuals in the third, second, and first (lowest) quartiles of LINE-1 methylation were 1.1 (95% confidence interval (CI) 0.7–1.8), 1.4 (95% CI 0.8–2.2), and 2.6 (95% CI 1.7–4.1) (P for trend <0.001), respectively, compared to individuals in the fourth (highest) quartile. A 1.9-fold (95% CI 1.4–2.6) increased risk of HCC was observed among individuals with LINE-1 methylation below the median compared to individuals with higher (>median) LINE-1 methylation. Our results demonstrate for the first time that individuals with global hypomethylation measured in LINE-1 repeats in blood leukocyte DNA have an increased risk for HCC. Our data provide the evidence that global hypomethylation detected in the easily obtainable DNA source of blood leukocytes may help identify individuals at risk of HCC.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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