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

Annekatrin Lukanova, Susen Becker, Anika Hüsing, Helena Schock, Veronika Fedirko, Elisabeth Trepo, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Vassiliki Benetou, Dimitrios Trichopoulos, Ute Nöthlings, Anne Tjønneland, Kim Overvad, Laure Dossus, Birgit Teucher, Heiner Boeing, Krasimira Aleksandrova, Domenico Palli, Valeria PalaSalvatore Panico, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-De-Mesquita, Peter D. Siersema, Petra H M Peeters, Jose Ramon Quiros, Eric J. Duell, Esther Molina-Montes, Maria Dolores Chirlaque, Aurelio Barricarte Gurrea, Miren Dorronsoro, Björn Lindkvist, Dorthe Johansen, Mårten Werner, Malin Sund, Kay Tee Khaw, Nick Wareham, Timothy J. Key, Ruth C. Travis, Sabina Rinaldi, Isabelle Romieu, Marc J. Gunter, Elio Riboli, Mazda Jenab, Rudolf Kaaks

Research output: Contribution to journalArticle


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), ptrend = 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.

Original languageEnglish
Pages (from-to)164-173
Number of pages10
JournalInternational Journal of Cancer
Issue number1
Publication statusPublished - Jan 1 2014



  • EPIC
  • hepatocellular carcinoma
  • insulin-like growth factor I
  • prospective study
  • sex hormone-binding globulin
  • testosterone

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lukanova, A., Becker, S., Hüsing, A., Schock, H., Fedirko, V., Trepo, E., Trichopoulou, A., Bamia, C., Lagiou, P., Benetou, V., Trichopoulos, D., Nöthlings, U., Tjønneland, A., Overvad, K., Dossus, L., Teucher, B., Boeing, H., Aleksandrova, K., Palli, D., ... Kaaks, R. (2014). Prediagnostic plasma testosterone, sex hormone-binding globulin, IGF-I and hepatocellular carcinoma: Etiological factors or risk markers? International Journal of Cancer, 134(1), 164-173.