TY - JOUR
T1 - Inflammatory and Metabolic Biomarkers and Risk of Liver and Biliary Tract Cancer
AU - Aleksandrova, Krasimira
AU - Boeing, Heiner
AU - Noethlings, Ute
AU - Jenab, Mazda
AU - Fedirko, Veronika
AU - Kaaks, Rudolf
AU - Lukanova, Annekatrin
AU - Trichopoulou, Antonia
AU - Trichopoulos, Dimitrios
AU - Boffetta, Paolo
AU - Trepo, Elisabeth
AU - Westhpal, Sabine
AU - Duarte-Salles, Talita
AU - Stepien, Magdalena
AU - Overvad, Kim
AU - Tjonneland, Anne
AU - Halkjaer, Jytte
AU - Boutron-Ruault, Marie-Christine
AU - Dossus, Laure
AU - Racine, Antoine
AU - Lagiou, Pagona
AU - Bamia, Christina
AU - Benetou, Vassiliki
AU - Agnoli, Claudia
AU - Palli, Domenico
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Vineis, Paolo
AU - Bueno-De-Mesquita, Bas
AU - Peeters, Petra H.
AU - Gram, Inger Torhild
AU - Lund, Eiliv
AU - Weiderpass, Elisabete
AU - Quiros, J. Ramon
AU - Agudo, Antonio
AU - Sanchez, Maria-Jose
AU - Gavrila, Diana
AU - Barricarte, Aurelio
AU - Dorronsoro, Miren
AU - Ohlsson, Bodil
AU - Lindkvist, Bjoern
AU - Johansson, Anders
AU - Sund, Malin
AU - Khaw, Kay-Tee
AU - Wareham, Nicholas
AU - Travis, Ruth C.
AU - Riboli, Elio
AU - Pischon, Tobias
PY - 2014
Y1 - 2014
N2 - 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-HMWadiponectin 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.
AB - 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-HMWadiponectin 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.
U2 - 10.1002/hep.27016
DO - 10.1002/hep.27016
M3 - Article
C2 - 24443059
SN - 1527-3350
VL - 60
SP - 858
EP - 871
JO - Hepatology
JF - Hepatology
IS - 3
ER -
