| OBJECTIVES:The studies of diabetes mellitus and hepatocellular carcinoma (HCC) reported inconsistent findings. The meta-analysis of case-control and cohort studies was conducted to examine the association between diabetes mellitus and risk of HCC.METHODS:Studies were identified by searching PUBMED, EMBASE and Cochrane Controlled Trials Register database up to December 2010 and the reference lists of retrieved articles. Pooled risk estimates were calculated using the random-effects model. Potential sources of heterogeneity were explored by subgroup analyses, and publication bias was evaluated using funnel plot and Egger's regression method.RESULTS:A total of 17 case-control studies and 25 cohort studies were included in the meta-analysis for the association of diabetes mellitus and HCC incidence. The combined risk estimate of all studies found a statistically significant increased risk of HCC incidence among diabetic individuals (RR=2.31; 95%CI:1.87,2.84). The pooled risk estimate of 17 case-control studies (OR=2.40; 95%CI:1.85,3.11) was slightly higher than the summary risk estimate from the 25 cohort studies (RR=2.23; 95% CI:1.68,2.96). In subgroup analyses, the pooled risk estimate was significantly higher for studies with general controls (RR=3.01; 95% CI:2.74,3.31) than those with hospital controls (RR=1.90; 95% CI:1.59,2.27). And the pooled RR for male subgroup (RR=2.03,95% CI:1.58,2.62) was slightly higher than female subgroup (RR=1.91; 95% CI:1.22,2.99). Individuals who had the longest duration of diabetes mellitus (>10 years) were most likely to develop HCC than individuals who had diabetes mellitus between 5 and 10 years or less than 5 years (pooled RR=3.26; 95% CI:2.17,4.91 vs 2.73; 95% CI:1.59,4.68 vs 2.62; 95% CI:1.59,4.33). The pooled risk estimates were 0.31 (95% CI:0.19,0.49) for patients receiving metformin treatment and 4.0 (95% CI:1.94,8.24) for individuals receiving sulfonylurea or insulin treatment. For studies adjusted for age and sex, hepatitis and BMI respectively, a lowered RR was identified. The pooled RR of 7 cohort studies found a statistically significant increased risk of HCC mortality (RR=2.43; 95% CI:1.66,3.55) among individuals with diabetes mellitus compared with non-diabetic individuals.CONCLUSION:This meta-analysis shows that diabetes mellitus is associated with moderately increased risk of HCC incidence, as well as HCC mortality. Metformin treatment is found with potentially protective effects against risk of HCC. On the contrary, long duration of diabetes mellitus and sulfonylurease or insulin treatment can increase the risk of HCC. Considering the rapidly increasing prevalence of diabetes mellitus, the study underlines the need for cancer prevention in diabetic individuals. |
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