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In recent years, increasing evidence has suggested a strong association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC). To provide a quantitative assessment of this association, we performed a systematic review and metaanalysis of cohort studies. We collected studies through a literature search of Medline from January 1, 1966 and EMBASE from January 1, 1974, through July 31, 2010. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. A total of 25 cohort studies that met our inclusion and exclusion criteria were included in our analysis. Among these, 18 studies showed that DM was associated with an increased incidence of HCC (SRRs 5 2.01, 95% CI: 1.61-2.51), compared with individuals without DM. There was a statistically significant heterogeneity among these studies (Q 5 136.68, p < 0.001, I 2 5 87.6%). Analyses subgrouped by controlling confounders revealed that the increased incidence of HCC was independent of geographic location, alcohol consumption, history of cirrhosis, or infections with hepatitis B (HBV) or hepatitis C virus (HCV). In addition, DM was also positively associated with HCC mortality (SRR 5 1.56; 95% CI: 1.30-1.87), with no significant evidence of heterogeneity among studies (Q 5 1.16, p 5 0.56, I 2 50%). There were no significant publication bias (p 5 0.79 for Egger's regression asymmetry test). These findings strongly support a positive association between DM and increased risk of HCC in both males and females.Hepatocellular carcinoma (HCC) is one of the most prevalent tumor types, with increased incidence and mortality in recent years. Annually, approximately 500,000 new cases are diagnosed worldwide and a nearly equivalent number die of this disease. Chronic infection with hepatitis B (HBV) or hepatitis C virus (HCV) has been considered the most important etiologic risk factors for human HCC. 1 In addition, excessive alcohol consumption, cigarette smoking, and environmental exposure to aflatoxin are also risk factors for HCC development. 2 However, many individuals who have been exposed to these risk factors never develop HCC, while 15-50% of cases occur among those without exposure. 3 Coinciding with increased HCC incidence, the prevalence of DM has also grown markedly over the past two decades in most countries. 4,5 In recent years, DM has become highly suspect as a risk factor for several malignancies, including cancers of the breast, 6 endometrium, 7 pancreas, 8 and liver. 9 A systematic review and meta-analysis of 26 studies (13 case-control and 13 cohort) conducted in 2005 showed that individuals with DM had a 2.5-fold greater risk of HCC [pooled odds ratio in caseÀcontrol studies ¼ 2.5; 95% confidence interval (CI): 1.8-3.5; pooled relative risk (RR) in cohort studies ¼ 2.5; 95% CI: 1.9-3.2] compared to controls. This significant association between diabetes and HCC was independent of alcohol consumption or hepatitis viral infections. 9 Since then, other relevant studies on the associat...

Increasing evidence suggests that a history of diabetes mellitus (DM) may be associated with an increased risk of colorectal cancer (CRC). To provide a quantitative assessment of the association between DM and risk of CRC, We evaluated the relation between DM and incidence and mortality of CRC in a systematic review of cohort studies. Full publications of cohort studies were identified in MEDLINE, EMBASE and Science Citation Index Expanded, through February 28, 2011. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were summarized using a random-effects model. Between-study heterogeneity was assessed using the Cochran's Q and I2 statistics. A total of 41 cohort studies (35 articles) were included in this systematic review. Combining 30 cohort studies which presented results on diabetes and CRC incidence, diabetes was associated with an increased incidence of CRC (SRRs 1.27, 95% CI: 1.21-1.34), with evident heterogeneity among studies (P=0.002, I2=48.4%). Subgroup analysis and meta-regression analysis by controlling the confounders showed that the increased incidence of CRC was independent of geographic locations, sex, family history of colorectal cancer, smoking, physical activity and body mass index. Diabetes was also positively associated with CRC mortality (SRR 1.20, 95% CI: 1.03-1.40), with evidence of heterogeneity between studies (P<0.001, I2=81.4%). Results from this systematic review support that compared to non-diabetic individuals, diabetic individuals have an increased risk of CRC.

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Serum IL-33 may be a useful biomarker for predicting the prognosis of gastric cancer.

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A major hallmark of pancreatic ductal adenocarcinoma (PDAC) is extensive local tumor invasion and early systemic dissemination. DJ-1 has been shown to prevent cell death via the Akt pathway, thereby playing an important role in cancer progression and Parkinson's disease development. Here, we investigated the role of DJ-1 in tumor invasion and metastasis of pancreatic cancer and showed that DJ-1 is upregulated in 68.5% of pancreatic cancer specimens, correlated with tumor stage and predictive of short overall survival. Knockdown of DJ-1 expression in two PDAC cell lines reduced cell migration and invasion potential in vitro and inhibited metastasis in vivo. Knockdown of DJ-1 led to cytoskeleton disruption and diminished urokinase plasminogen activator (uPA) activity and expression, without affecting plasminogen activator inhibitor-1 and uPA receptor (uPAR) expression. All these effects were reversed by restoration of DJ-1 expression. In determining the pathway through which DJ-1 regulated cell migration and invasion, DJ-1 was found not to regulate Akt phosphorylation. Rather, it promoted extracellular signal-regulated kinase (ERK) and SRC phosphorylation. Inhibition of the ERK pathway in PDAC mimicked the effects of DJ-1 on cell migration, invasion, actin cytoskeleton and uPA/uPAR system and abolished the effects on promoting PDAC cell invasion and migration. These data represent the first identification of an important function of DJ-1, which is to regulate the invasion and metastasis properties of PDAC through the ERK/uPA cascade.