• Open Access

Association of mitochondrial DNA content in peripheral blood leukocyte with hepatitis B virus-related hepatocellular carcinoma in a Chinese Han population

Authors

  • Siyuan Zhao,

    1. Department of Interventional Radiology, Tangdu Hospital
    2. State Key Laboratory of Cancer Biology and Department of Cell Biology and Cell Engineering Research Center, Fourth Military Medical University, Xi’an
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    • These authors contributed equally to this work.

  • Yefa Yang,

    1. Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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    • These authors contributed equally to this work.

  • Juan Liu,

    1. State Key Laboratory of Cancer Biology and Department of Cell Biology and Cell Engineering Research Center, Fourth Military Medical University, Xi’an
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  • Hanqiang Liu,

    1. State Key Laboratory of Cancer Biology and Department of Cell Biology and Cell Engineering Research Center, Fourth Military Medical University, Xi’an
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  • Naijian Ge,

    1. Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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  • Hushan Yang,

    1. Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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  • Hongxin Zhang,

    Corresponding author
    1. Department of Interventional Radiology, Tangdu Hospital
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  • Jinliang Xing

    Corresponding author
    1. State Key Laboratory of Cancer Biology and Department of Cell Biology and Cell Engineering Research Center, Fourth Military Medical University, Xi’an
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5To whom correspondence should be addressed.
E-mail: xingjl@fmmu.edu.cn; zhhxtdjr@163.com

Abstract

Increasing epidemiological evidence has indicated that inherited variations of mtDNA content could affect the genetic susceptibility of many malignancies in a tumor-specific manner. However, the association between mtDNA content and hepatocellular carcinoma (HCC) remains undetermined. In this study, mtDNA content of peripheral blood leukocytes was determined using quantitative real-time PCR in a case–control study consisting of 274 HCC cases, 126 non-cancer patient controls with chronic liver diseases (CLD), and 258 healthy controls. We found that HCC cases had a significant lower mtDNA content than CLD controls (median [range]: 0.77 [0.17–2.30] vs 0.84 [0.32–3.37]; P = 0.012) and healthy controls (0.77 [0.17–2.30] vs 0.84 [0.35–3.44]; P = 0.035). There was no difference in mtDNA content between CLD and healthy controls (0.84 [0.32–3.37] vs 0.84 [0.35–3.44]; P = 0.261). We further assessed the association between mtDNA content and HCC and found that, compared to individuals with high mtDNA content, those with low mtDNA content had a significantly increased risk of HCC when health controls (adjusted odds ratio [aOR] = 1.64, 95% confidence interval [CI] = 1.06–2.55), CLD controls (aOR = 1.57, 95% CI = 1.10–2.25) or combined controls (aOR = 1.55, 95% CI = 1.12–2.14) were used as reference. In addition, stratified analyses showed that the significant association was only evident in younger individuals, male individuals, ever-smokers, and never-drinkers. Collectively, our findings provided the first epidemiological evidence that mtDNA content in peripheral blood leukocytes is significantly associated with HCC, which warrants further validation in prospective studies. (Cancer Sci 2011; 102: 1553–1558)

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