Background: Diabetes has been associated with an increa- sed risk of hepatocellular carcinoma (HCC) in studies of referred patients. Th is is the first population based case control study in the USA to examine this a ssociation while adjusting for other major risk factors related to HCC. Methods: We used the Surveillance Epidemiology and End-Results Program (SEER)Medicare l inked database to identify patients aged 65 years and older diagnosed with HCC a nd randomly selected non-cancer controls between 1994 and 1999. Only cases and controls with continuous Medicare enrolment for three years prior to the index d ate were examined. Inpatient and outpatient claims files were searched for diagn ostic codes indicative of diabetes,hepatitis C virus (HCV), hepatitis B virus (H BV), alcoholic liver disease, and haemochromatosis. HCC patients without these c onditions were categorised as idiopathic. Unadjusted and adjusted odds ratios we re calculated in logistic regression analyses. Results: We identified 2061 HCC p atients and 6183 non-cancer controls. Compared with non-cancer controls, patie nts with HCC were male (66%v 36%) and non-White (34%v 18%). The proportion of HCC patients with diabetes (43%) was significantly greater than non-cancer controls (19%). In multiple logistic regression analyses that adjusted for demo graphics features and other HCC risk factors (HCV, HBV, alcoholic liver disease, and haemochromatosis),diabetes was associated with a threefold increase in the risk of HCC. In a subset of patients without these major risk factors, the adjus ted odds ratio for diabetes declined but remained significant (adjusted odds rat io 2.87 (95%con-fidence interval 2.49-3.30)). A significant positive interact ion between HCV and diabetes was detected (p< 0.0001). Similar findings persiste d in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis. Conclusions:Diabetes is associated with a 2-3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk factors. Findings from this population based study suggest that diabetes is an independen t risk factor for HCC.
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