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Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer
Author(s) -
Aleksandrova Krasimira,
Boeing Heiner,
Nöthlings Ute,
Jenab Mazda,
Fedirko Veronika,
Kaaks Rudolf,
Lukanova Annekatrin,
Trichopoulou Antonia,
Trichopoulos Dimitrios,
Boffetta Paolo,
Trepo Elisabeth,
Westhpal Sabine,
DuarteSalles Talita,
Stepien Magdalena,
Overvad Kim,
Tjønneland Anne,
Halkjær Jytte,
BoutronRuault MarieChristine,
Dossus Laure,
Racine Antoine,
Lagiou Pagona,
Bamia Christina,
Benetou Vassiliki,
Agnoli Claudia,
Palli Domenico,
Panico Salvatore,
Tumino Rosario,
Vineis Paolo,
BuenodeMesquita Bas,
Peeters Petra H.,
Gram Inger Torhild,
Lund Eiliv,
Weiderpass Elisabete,
Quirós J. Ramón,
Agudo Antonio,
Sánchez MaríaJosé,
Gavrila Diana,
Barricarte Aurelio,
Dorronsoro Miren,
Ohlsson Bodil,
Lindkvist Björn,
Johansson Anders,
Sund Malin,
Khaw KayTee,
Wareham Nicholas,
Travis Ruth C.,
Riboli Elio,
Pischon Tobias
Publication year - 2014
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.27016
Subject(s) - medicine , adiponectin , gastroenterology , hepatocellular carcinoma , obesity , liver cancer , insulin resistance
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. (H epatology 2014;60:858–871)