title: Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection.
abstract: Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 × 10(-5)). Compared to HBV patients with higher mtDNA content, those with lower mtDNA content had a significantly increased risk of HCC with an odds ratio (OR) of 2.19 (95% confidence interval [CI] 1.28-3.72, P = 0.004). Quartile analyses revealed a significant dose-dependent effect (Ptrend = 0.001) for this association. In a pilot longitudinal sub-cohort of 14 matched cases-control pairs, we observed a trend of dramatically decreased mtDNA content in cases and slightly decreased mtDNA content in controls, with a significant interaction of case-control status with time (Pinteraction = 0.049). Our findings suggest that circulating mtDNA is a potential novel non-invasive biomarker of HCC risk in HBV patients.
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Hie-Won
authors.initials: HW
authors.lastname: Hann
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.|Institute of Pharmacy, Pharmaceutical College, Henan University, Kaifeng, Henan 475004, China.
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wan
authors.affiliation: Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hann
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.|Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226000, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Xishan
authors.initials: X
authors.lastname: Ye
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Evans
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Myers
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Center for Human Genetics Research, Department of Molecular Physiology &Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Bingshan
authors.initials: B
authors.lastname: Li
authors.affiliation: Experimental Teaching Center, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000097:blood*; D004326:Drinking; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000209:etiology*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking
chemical_list: D004272:DNA, Mitochondrial