1From the Graduate Institute of Medical Science (C-IC); Center of Excellence for Cancer Research (C-IC, Y-AF); Cancer Center (C-IC), Wan Fang Hospital, Taipei Medical University, Taipei; Department of Health care Administration (C-FK), Central Taiwan University of Science and Technology, Taichung; Graduate Institute of Toxicology (S-HL), College of Medicine, National Taiwan University, Taipei; Division of Cardiovascular Medicine (J-CL), Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City; Department of Ophthalmology (L-LW), National Taiwan University Hospital; Section of Endocrinology and Metabolism (C-JC), Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei; Institute of Biomedical Informatics (H-CY), National Yang Ming University; Department of Biochemistry (JH), School of Medicine, Taipei Medical University, Taipei, Taiwan; City of Hope National Medical Center (JSM), Duarte, CA; College of Medical Science and Technology (JSM), Taipei Medical University; Graduate Institute of Toxicology (SYW), College of Medicine, National Taiwan University, Taipei; Department of Internal Medicine (SYW), School of Medicine, College of Medicine; Department of Radiation Oncology (SYW), Wan Fang Hospital, Taipei Medical University, Taipei; Department of Biotechnology (SYW), Hung Kuang University, Taichung, Taiwan.
Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an increased incidence of nonliver cancers. Taking statin or metformin may decrease inflammation and infiltration, which may, as a result, reduce the risk of liver cancer or other major cancers in patients with HBV infection. The purpose of this study was to evaluate the hypothesis that statin and metformin could reduce the incidence of liver cancer (HCC) or nonliver cancers in patients with HBV.Using the Taiwan Longitudinal Health Insurance Database 2000 to 2008, this cohort study comprised patients with a recorded diagnosis of HBV (N = 71,847) between January 1, 2000 and December 31, 2008. Each patient was followed-up until the end of 2008. The occurrence of HCC or a nonliver cancer was evaluated in patients who either were or were not taking statin or metformin. Cox proportional hazard regressions were used to evaluate the cancer incidence after adjusting for known confounding factors.In total, 71,824 HBV-infected patients comprised the study cohort. Our study showed that either metformin or statin use was associated with a reduction in the incidence of cancer. This was most prominent in patients taking both statin and metformin. The adjusted hazard ratios (HRs) for patients using only statin were 0.52 (95% confidence interval [CI], 0.48-0.57) for all cancers, 0.28 (95% CI, 0.23-0.35) for liver cancer, and 0.63 (95% CI, 0.57-0.70) for nonliver cancers. Patients taking only metformin had risk-adjusted HRs of 0.82 (95% CI, 0.75-0.90) for all cancers, 0.97 (95% CI, 0.84-1.14) for liver cancer, and 0.75 (95% CI, 0.67-0.84) for nonliver cancers. A dose-dependent effect of statin use for chemoprevention was observed for all cancers, including both liver cancer and nonliver cancers. A dose-dependent effect of metformin was also seen in liver cancer and nonliver cancers without stratification into different cumulative daily doses of statin use.This population-based cohort study investigated the protective effect of statin and metformin against cancer events in patients with HBV infection. Our study demonstrated that either statin or metformin served as independent chemopreventive agents with a dose-response effect in reducing the incidence of cancer with a dose-response effect of the agents and an additive or synergistic effect of combining statin and metformin use in reducing the incidence of many cancers.