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Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer

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Official URL:https://doi.org/10.1002/hep.27016
PubMed:View item in PubMed
Creators Name:Aleksandrova, K. and Boeing, H. and Noethlings, U. and Jenab, M. and Fedirko, V. and Kaaks, R. and Lukanova, A. and Trichopoulou, A. and Trichopoulos, D. and Boffetta, P. and Trepo, E. and Westhpal, S. and Duarte-Salles, T. and Stepien, M. and Overvad, K. and Tjonneland, A. and Halkjaer, J. and Boutron-Ruault, M.C. and Dossus, L. and Racine, A. and Lagiou, P. and Bamia, C. and Benetou, V. and Agnoli, C. and Palli, D. and Panico, S. and Tumino, R. and Vineis, P. and Bueno-de-Mesquita, B. and Peeters, P.H. and Gram, I.T. and Lund, E. and Weiderpass, E. and Quiros, J.R. and Agudo, A. and Sanchez, M.J. and Gavrila, D. and Barricarte, A. and Dorronsoro, M. and Ohlsson, B. and Lindkvist, B. and Johansson, A. and Sund, M. and Khaw, K.T. and Wareham, N. and Travis, R.C. and Riboli, E. and Pischon, T.
Journal Title:Hepatology
Journal Abbreviation:Hepatology
Volume:60
Number:3
Page Range:858-871
Date:September 2014
Keywords:Hepatocellular Carcinoma, Bile Duct Cancer, Inflammation, Hyperinsulinemia, Biomarkers
Abstract:Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n = 125), GBTC (n = 137), or IBD (n = 34). Using risk-set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide, and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95% CI = 1.02-1.46; P = 0.03; 1.90; 95% CI = 1.30-2.77; P = 0.001; 2.25; 95% CI = 1.43-3.54; P = 0.0005; and 2.09; 95% CI = 1.19-3.67; P = 0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95% CI = 1.05-1.42; P = 0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95% CI = 1.25-2.11; P = 0.0003) and IBD (IRR = 10.5; 95% CI = 2.20-50.90; P = 0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.
ISSN:0270-9139
Publisher:Wiley (U.S.A.)
Additional Information:Author' reply in: Hepatology 62(1): 320-321.
Item Type:Article

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