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

Lukanova, Annekatrin; Becker, Susen; Huesing, Anika; Schock, Helena; Fedirko, Veronika; Trepo, Elisabeth; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona and Benetou, Vassiliki, et al. (2014) In International Journal of Cancer 134(1). p.164-173
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... (More)
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. (Less)
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keywords
hepatocellular carcinoma, testosterone, sex hormone-binding globulin, insulin-like growth factor I, prospective study, EPIC
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International Journal of Cancer
volume
134
issue
1
pages
164 - 173
publisher
John Wiley & Sons
external identifiers
  • wos:000325982000017
  • scopus:84885949204
ISSN
0020-7136
DOI
10.1002/ijc.28342
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English
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68a1d154-988f-46a4-beb8-c288911e0632 (old id 4204264)
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@article{68a1d154-988f-46a4-beb8-c288911e0632,
  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. (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.},
  author       = {Lukanova, Annekatrin and Becker, Susen and Huesing, Anika and Schock, Helena and Fedirko, Veronika and Trepo, Elisabeth and Trichopoulou, Antonia and Bamia, Christina and Lagiou, Pagona and Benetou, Vassiliki and Trichopoulos, Dimitrios and Noethlings, Ute and Tjonneland, Anne and Overvad, Kim and Dossus, Laure and Teucher, Birgit and Boeing, Heiner and Aleksandrova, Krasimira and Palli, Domenico and Pala, Valeria and Panico, Salvatore and Tumino, Rosario and Ricceri, Fulvio and Bueno-De-Mesquita, H. Bas and Siersema, Peter D. and Peeters, Petra H. M. and Quiros, Jose Ramon and Duell, Eric J. and Molina-Montes, Esther and Chirlaque, Maria-Dolores and Gurrea, Aurelio Barricarte and Dorronsoro, Miren and Lindkvist, Bjoern and Johansen, Dorthe and Werner, Marten and Sund, Malin and Khaw, Kay-Tee and Wareham, Nick and Key, Timothy J. and Travis, Ruth C. and Rinaldi, Sabina and Romieu, Isabelle and Gunter, Marc J. and Riboli, Elio and Jenab, Mazda and Kaaks, Rudolf},
  issn         = {0020-7136},
  keyword      = {hepatocellular carcinoma,testosterone,sex hormone-binding globulin,insulin-like growth factor I,prospective study,EPIC},
  language     = {eng},
  number       = {1},
  pages        = {164--173},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Prediagnostic plasma testosterone, sex hormone-binding globulin, IGF-I and hepatocellular carcinoma: Etiological factors or risk markers?},
  url          = {http://dx.doi.org/10.1002/ijc.28342},
  volume       = {134},
  year         = {2014},
}