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

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.