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

Krasimira Aleksandrova, Heiner Boeing, Ute Nöthlings, Mazda Jenab, Veronika Fedirko, Rudolf Kaaks, Annekatrin Lukanova, Antonia Trichopoulou, Dimitrios Trichopoulos, Paolo Boffetta, Elisabeth Trepo, Sabine Westhpal, Talita Duarte-Salles, Magdalena Stepien, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Marie Christine Boutron-Ruault, Laure Dossus, Antoine RacinePagona Lagiou, Christina Bamia, Vassiliki Benetou, Claudia Agnoli, Domenico Palli, Salvatore Panico, Rosario Tumino, Paolo Vineis, Bas Bueno-de-Mesquita, Petra H. Peeters, Inger Torhild Gram, Eiliv Lund, Elisabete Weiderpass, J. Ramón Quirós, Antonio Agudo, María José Sánchez, Diana Gavrila, Aurelio Barricarte, Miren Dorronsoro, Bodil Ohlsson, Björn Lindkvist, Anders Johansson, Malin Sund, Kay Tee Khaw, Nicholas Wareham, Ruth C. Travis, Elio Riboli, Tobias Pischon

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)858-871
Number of pages14
JournalHepatology
Volume60
Issue number3
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Hepatology

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