Abstract
Background: Emerging epidemiologic data suggest that cigarette smoking may increase the risk of primary liver cancer. We evaluated this association based on a systematic review of epidemiologic evidence among Japanese populations. Methods: Original data were obtained from MEDLINE searches using PubMed, complemented with manual searches. The evaluation was performed in terms of the magnitude of association (‘strong’, ‘moderate’, ‘weak’ or ‘no association’) in each study and the strength of evidence (‘convincing’, ‘probable’, ‘possible’ or ‘insufficient’), together with biological plausibility as previously done by the International Agency for Research on Cancer. Results: A total of 12 cohort studies and 11 case–control studies were identified. Nine cohort studies (two with adjustment for hepatitis B and C virus infections and seven without it) reported weak to strong positive associations between smoking and liver cancer, with dose–response relationships shown in three studies. Five case–controls studies (three with the virus adjustment and two without it) demonstrated such positive associations, with a dose–response relationship shown in only one study, while in six case–control studies, the observed associations were judged to be of the lowest magnitude or inverse due to the lack of any dose–response relationship. Conclusion: We conclude that cigarette smoking ‘probably’ increases the risk of primary liver cancer among the Japanese. Potential confounding by hepatitis virus infection and virus–smoking interactions need to be addressed in future studies.