Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 134, Issue 1, Pages 164-173Publisher
WILEY
DOI: 10.1002/ijc.28342
Keywords
hepatocellular carcinoma; testosterone; sex hormone-binding globulin; insulin-like growth factor I; prospective study; EPIC
Categories
Funding
- French National Cancer Institute (Institut National du Cancer, INCA) [2009-139]
- European Commission: Public Health and Consumer Protection Directorate
- European Commission: International Agency for Research on Cancer (IARC)
- Danish Cancer Society (Denmark)
- Ligue Contre le Cancer
- Institut Gustave Roussy
- Mutuelle Generale de l'Education Nationale
- Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
- Deutsche Krebshilfe
- Deutsches Krebsforschungszentrum
- Federal Ministry of Education and Research (Germany)
- Hellenic Health Foundation
- J.F. Costopoulos Foundation (Greece)
- Italian Association for Research on Cancer (AIRC)
- National Research Council
- AIRE-ONLUS Ragusa
- AVIS Ragusa and Sicilian Government (Italy)
- Dutch Ministry of Public Health, Welfare and Sports (VWS)
- Netherlands Cancer Registry (NKR)
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands (The Netherlands)
- Nordforsk
- Nordic Center of Excellence programme on Food, Nutrition and Health (Norway)
- Health Research Fund (FIS)
- Regional Government of Andalucia
- Regional Government of Asturias
- Regional Government of Basque Country
- Regional Government of Murcia [6236]
- Regional Government of Navarra
- Regional Government of ISCIII RETIC (Spain) [RD06/0020]
- Swedish Cancer Society
- Swedish Scientific Council
- Regional Government of Skane and Vosterbotten (Sweden)
- Cancer Research UK
- Medical Research Council
- Stroke Association
- British Heart Foundation
- Department of Health
- Food Standards Agency
- Wellcome Trust (United Kingdom)
- [ERC-2009-AdG 232997]
- Cancer Research UK [16491, 14136] Funding Source: researchfish
- Medical Research Council [G0401527, G1000143, MC_UU_12015/1, MC_U106179471] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10135] Funding Source: researchfish
- MRC [MC_UU_12015/1] Funding Source: UKRI
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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. (c) 2013 UICC What's new? Testosterone and insulin-like growth factor-1 (IGF-1) are implicated in the development of hepatocellular carcinoma (HCC), though their involvement may be more complex than previously thought. Here, in a unique study population with low prevalence of hepatitis infections, an association was detected between HCC risk and increased levels of sex hormone binding globulin (SHBG) and IGF-1 prior to diagnosis. Neither testosterone nor IGF-1, however, was found to have an etiological influence in the decade before diagnosis. The results suggest that SHBG and IGF-I should be considered in the clinical evaluation of patients at increased risk of HCC.
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