Prediagnostic plasma testosterone, sex hormone‐binding globulin, IGF‐I and hepatocellular carcinoma: Etiological factors or risk markers?

Year: 2013

Type: article

Abstract: Elevated prediagnostic testosterone and insulin-like growth factor I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone-binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk [OR for top versus bottom tertile of 3.86 (1.32-11.3), p(trend) = 0.009]. As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p = 0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with prediagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as prediagnostic risk marker for HCC.

Source: International Journal of Cancer

DOI: 10.1002/ijc.28342

Institutions: German Cancer Research Center, Umeå University, University Hospital Leipzig, Leipzig University, Emory University, Centre international de recherche sur le cancer, National and Kapodistrian University of Athens, Hellenic Health Foundation, Harvard University, Academy of Athens, University of Bonn, Christian-Albrechts-Universität zu Kiel, Danish Cancer Society, Aarhus University, Inserm, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, German Institute of Human Nutrition, Istituto per lo Studio e la Prevenzione Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Federico II University Hospital, University of Naples Federico II, Italian institute for Genomic Medicine, University Medical Center Utrecht, National Institute for Public Health and the Environment, Imperial College London, Gobierno del Principado de Asturias, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Andalusian School of Public Health, Servicio Murciano de Salud, Biogipuzkoa Health Research Institute, University of Gothenburg, Skåne University Hospital, University Hospital of Umeå, University of Cambridge, Addenbrooke's Hospital, MRC Epidemiology Unit, Medical Research Council, University of Oxford

Language: English

Topic: Hepatocellular Carcinoma Treatment and Prognosis

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W1496823095