Corrigendum to: “Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma” [J Hepatol 2012;57:69–76]

Department of Internal Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.
Journal of Hepatology (Impact Factor: 11.34). 03/2012; 57(1):69-76. DOI: 10.1016/j.jhep.2012.02.022
Source: PubMed


Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions.
We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated.
Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias.
Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers.

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    ABSTRACT: The highest incidence of Cholangiocarcinoma (CCA), a malignancy of bile duct epithelia, is in the Northeast of Thailand. The liver fluke, Opisthorchis viverrini, is the known risk factor for CCA development in this region. Approximately 1% of O. viverrini infected individuals develop CCA. There could be other factors that influence the cholangiocarcinogenesis particularly in the O. viverrini infected individuals. The global epidemiological studies of risk factors for CCA in non-O. viverrini related patients indicated diabetes mellitus (DM) as a risk factor of CCA. The molecular studies in many cancers indicated that high levels of glucose, insulin and an obese condition directly and indirectly enhanced growth of cancers. For O. viverrini associated CCA, there is limited information related to DM and CCA development. High mortality rates of CCA and DM, however, were reported in the same geographical areas of northeastern Thailand. Whether DM is a factor that enhances CCA development in O. viverrini infected individuals or promotes CCA progression are discussed in a perspective of epidemiological and molecular studies. Copyright © 2015 Elsevier Ltd. All rights reserved.
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    • "5,10-Methylenetetrahydrofolate reductase MTHFR Involved in folate metabolism and DNA methylation [223] Thymidylate synthase TS Associated with DNA repair Family of detoxification enzymes [223] Glutathione S-transferases GST01 [224] Multidrug resistance-associated protein 2 MRP2/ABC2 Biliary transporter involved in clearing biliary toxins Biliary transporter involved in trafficking [225] ATP8B1 FIC1 phosphotidylserine in cellular membranes [226] Natural killer cell receptor in PSC patients NKG2D Role in activating NK cells, key for tumor surveillance [227] X-ray repair cross-complementing group 1 XRCC1 Involved in DNA repair An inflammatory mediator pro-inflammatory enzymes [228] Prostaglandin-endoperoxide synthase 2/cyclooxygenase-2 PTGS2, COX-2 [229] Heterozygosity for the alpha1-antitrypsin Z allele A protease inhibitor which protects against [230] Guidelines indicate common genomic traits between iCCA and HCC, supporting the hypothesis of common cell ancestors in specific molecular subclasses: (1) Transcriptome analysis suggests that the poor prognostic subclass of iCCA shares genomic traits and signatures of poor prognosis of HCC [58] [60] [61], which are associated with stem-like molecular signatures [62] [63]; (2) iCCA and HCC share common copy number variations including gains (1q, 8q, and 17q) and losses (4q, 8p, 13q, and 17p) of arms and high-level amplifications of 11q 13 [58] [60] [64]; and (3) iCCA shares dominant risk factors associated with HCC development, including cirrhosis , HBV and HCV infections, and metabolic syndrome due to diabetes and/or obesity [34] [57]. "
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    • "Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) are the two most common primary liver cancers worldwide [1] and are malignancies that arise from epithelial cells that share an early common developmental program. The risk of developing CCA has been linked to liver flukes and primary sclerosing cholangitis (PSC), although most cases are thought to be sporadic with chronic inflammation as a likely risk factor [2]. Cirrhosis is the primary risk factor for HCC, and results from a chronic inflammatory fibrotic milieu. "
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