The Association Between Diabetes and Hepatocellular Carcinoma: A Systematic Review of Epidemiologic Evidence

El–Serag, Hashem B.; Hampel, Howard; Javadi, Fariba

doi:10.1016/j.cgh.2005.12.007

Cited by 729 publications

(505 citation statements)

References 40 publications

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“…HBV infection is a well-established risk factor for HCC, although the underlying molecular mechanisms and pathways remain to be defined (Pan et al 2011). Recent studies have established that diabetes is strongly associated with increased risk of HCC (El-Serag et al 2006). In an observational study, the authors reported a synergistic effect between diabetes and HBV infection on the risk of incident HCC (Ko et al 2012).…”

Section: Discussionmentioning

confidence: 88%

“…Diabetes is associated with increased risk of a spectrum of cancers (Yang et al 2012b) with a linear relationship between HbA1c and all-site cancer risk (Yang et al 2010a). In most surveys, among site-specific cancers, HCC ranks second in terms of strength of association with diabetes (El-Serag et al 2006), only preceded by pancreatic cancer (Everhart & Wright 1995).…”

Section: Introductionmentioning

confidence: 99%

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Enhancers and attenuators of risk associations of chronic hepatitis B virus infection with hepatocellular carcinoma in type 2 diabetes

Yang¹,

Wang²,

Luk³

et al. 2012

Endocrine-Related Cancer

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Chronic hepatitis B virus (HBV) infection promotes hepatocellular carcinoma (HCC) risk.In type 2 diabetes (T2D), use of insulin and statins was associated with reduced cancer risk while co-presence of low LDL cholesterol (LDLC !2.8 mmol/l) plus low triglyceride (TG; !1.7 mmol/l) increased cancer risk. There is experimental evidence showing that insulin insufficiency might promote HCC. In this study, we examined whether this lipid subphenotype and use of insulin or statins might modify the promoting effect of chronic HBV infection (indicated by the presence of hepatitis B surface antigen) on HCC. We analyzed data of 1319 T2D patients enrolled into the Hong Kong Diabetes Registry from December 1996 to January 2005 and followed up to 2005. Additive interaction was estimated using relative excess risk due to interaction and attributable proportion due to interaction. During 5782 person-years of follow-up, 1.74% (nZ23) of patients developed HCC (incidence, 3.98; 95% confidence interval, 2.36-5.60/1000 person-years). HbA1c R7.0% and the lipid phenotype (LDLC !2.8 mmol/l plus TG !1.7 mmol/l) increased the hazard ratios (HRs) of chronic HBV infection for HCC from 3.74 to 74.96 and from 11.01 to 89.82 respectively with significant interactions. Use of insulin or statins decreased the HRs from 37.51 to 5.87 and from 64.94 to 16.99 respectively with significant interactions (all P values !0.05). These findings support our hypothesis that hyperglycemia and co-presence of low LDLC plus low TG might enhance, while insulin or statin usage might attenuate the promoting effect of chronic HBV infection on HCC in T2D.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Enhancers and attenuators of risk associations of chronic hepatitis B virus infection with hepatocellular carcinoma in type 2 diabetes

Yang¹,

Wang²,

Luk³

et al. 2012

Endocrine-Related Cancer

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show abstract

“…An important report measuring DNA adducts of 4-aminobiphenyl, a hepatic carcinogen showed a significant increase in HCC risk with increasing levels of adducts [27]. Diabetes increases the risk of HCC, as shown by the first population-based study to assess the risk of HCC in diabetic patients [28]. An increased risk of cancer mortality in general has long been associated with obesity [29].…”

Section: Introductionmentioning

confidence: 99%

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma

Subramaniam

Shanmugam

Perumal

et al. 2013

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

197

229

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a b s t r a c t a r t i c l e i n f oHepatocellular carcinoma (HCC) is one of the most lethal malignancies, and is also the fourth most common cancer worldwide with around 700,000 new cases each year. Currently, first line chemotherapeutic drugs used for HCC include fluorouracil, cisplatin, doxorubicin, paclitaxel and mitomycin, but most of these are non-selective cytotoxic molecules with significant side effects. Sorafenib is the only approved targeted therapy by the U.S. Food and Drug Administration for HCC treatment, but patients suffer from various kinds of adverse effects, including hypertension. The signal-transducer-and-activator-of-transcription 3 (STAT3) protein, one of the members of STATs transcription factor family, has been implicated in signal transduction by different cytokines, growth factors and oncogenes. In normal cells, STAT3 activation is tightly controlled to prevent dysregulated gene transcription, whereas constitutively activated STAT3 plays an important role in tumorigenesis through the upregulation of genes involved in anti-apoptosis, proliferation and angiogenesis. Thus, pharmacologically safe and effective agents that can block STAT3 activation have the potential both for the prevention and treatment of HCC. In the present review, we discuss the possible role of STAT3 signaling cascade and its interacting partners in the initiation of HCC and also analyze the role of various STAT3 regulated genes in HCC progression, inflammation, survival, invasion and angiogenesis.

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“…Diabetes and obesity have both been identified as emerging risk factors for HCC because of their being risk factors for NASH. 66,67 NASH can result in cirrhosis, and it is thought to be responsible for a significant proportion of cryptogenic cirrhosis and HCC. 68,69 AI/AN in all regions have a higher prevalence of obesity than NHW and AI/AN have an elevated prevalence of diabetes.…”

Section: Discussionmentioning

confidence: 99%

Primary liver cancer incidence among American Indians and Alaska Natives, US, 1999-2004

Jim

Perdue

Richardson

et al. 2008

Cancer

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The Association Between Diabetes and Hepatocellular Carcinoma: A Systematic Review of Epidemiologic Evidence

Cited by 729 publications

References 40 publications

Enhancers and attenuators of risk associations of chronic hepatitis B virus infection with hepatocellular carcinoma in type 2 diabetes

Enhancers and attenuators of risk associations of chronic hepatitis B virus infection with hepatocellular carcinoma in type 2 diabetes

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma

Primary liver cancer incidence among American Indians and Alaska Natives, US, 1999-2004

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