Diabetes Mellitus and Liver Cancer Risk: An Evaluation Based on a Systematic Review of Epidemiologic Evidence among the Japanese Population

Objective: The potential associations of diabetes mellitus with malignant neoplasms including liver cancer have become a great concern from both clinical and preventive perspectives. Although sufficient evidence for a positive association between diabetes and liver cancer already exists, it would be informative to summarize up-to-date epidemiologic data in Japan. Methods: We systematically reviewed epidemiologic studies on diabetes and liver cancer among Japanese populations. Original data were obtained by searching the MEDLINE (PubMed) and Ichushi databases, complemented with manual searches. The evaluation was performed in terms of the magnitude of association in each study and the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient'), together with biological plausibility. Results: We identified 19 cohort studies, one pooled-analysis of seven cohort studies, and seven case-control studies. Of 24 relative risk estimates of liver cancer for diabetes reported in those cohort studies, 17 showed a weak to strong positive association, six revealed no association and one demonstrated a weak inverse association (summary relative risk 2.10, 95% confidence interval 1.60-2.76). Ten relative risk estimates from the case-control studies showed a weak to strong positive association (n = 9) or no association (n = 1; summary relative risk 2.32, confidence interval 1.73-3.12). Overall, the summary relative risk became 2.18 (confidence interval 1.78-2.69). Heterogeneity in relative risks was significant for the difference in categories of study population (P = 0.01), but not in study type (P = 0.39) or sex (P = 0.33). Conclusions: Diabetes mellitus 'probably' increases the risk of liver cancer among the Japanese population.