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Prediagnostic plasma testosterone, sex hormone‐binding globulin, IGF‐I and hepatocellular carcinoma: Etiological factors or risk markers?
Author(s) -
Lukanova Annekatrin,
Becker Susen,
Hüsing Anika,
Schock Helena,
Fedirko Veronika,
Trepo Elisabeth,
Trichopoulou Antonia,
Bamia Christina,
Lagiou Pagona,
Benetou Vassiliki,
Trichopoulos Dimitrios,
Nöthlings Ute,
Tjønneland Anne,
Overvad Kim,
Dossus Laure,
Teucher Birgit,
Boeing Heiner,
Aleksandrova Krasimira,
Palli Domenico,
Pala Valeria,
Panico Salvatore,
Tumino Rosario,
Ricceri Fulvio,
BuenodeMesquita H. Bas,
Siersema Peter D.,
Peeters Petra H.M.,
Quiros Jose Ramon,
Duell Eric J.,
MolinaMontes Esther,
Chirlaque MariaDolores,
Gurrea Aurelio Barricarte,
Dorronsoro Miren,
Lindkvist Björn,
Johansen Dorthe,
Werner Mårten,
Sund Malin,
Khaw KayTee,
Wareham Nick,
Key Timothy J.,
Travis Ruth C.,
Rinaldi Sabina,
Romieu Isabelle,
Gunter Marc J.,
Riboli Elio,
Jenab Mazda,
Kaaks Rudolf
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28342
Subject(s) - sex hormone binding globulin , medicine , endocrinology , hepatocellular carcinoma , testosterone (patch) , odds ratio , risk factor , european prospective investigation into cancer and nutrition , prospective cohort study , hormone , androgen
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. © 2013 UICC