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Inflammatory and Metabolic Biomarkers and Risk of Liver and Biliary Tract Cancer

Aleksandrova, Krasimira; Boeing, Heiner; Noethlings, Ute; Jenab, Mazda; Fedirko, Veronika; Kaaks, Rudolf; Lukanova, Annekatrin; Trichopoulou, Antonia; Trichopoulos, Dimitrios and Boffetta, Paolo, et al. (2014) In Hepatology 60(3). p.858-871
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,... (More)
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. (Less)
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published
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Hepatology
volume
60
issue
3
pages
858 - 871
publisher
John Wiley & Sons
external identifiers
  • wos:000341239200014
  • scopus:84906794845
ISSN
1527-3350
DOI
10.1002/hep.27016
language
English
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yes
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8ef6fa3c-f824-444c-9d98-a720c30b4f66 (old id 4713943)
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2014-11-03 07:16:01
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2017-10-22 04:24:20
@article{8ef6fa3c-f824-444c-9d98-a720c30b4f66,
  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-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.},
  author       = {Aleksandrova, Krasimira and Boeing, Heiner and Noethlings, Ute and Jenab, Mazda and Fedirko, Veronika and Kaaks, Rudolf and Lukanova, Annekatrin and Trichopoulou, Antonia and Trichopoulos, Dimitrios and Boffetta, Paolo and Trepo, Elisabeth and Westhpal, Sabine and Duarte-Salles, Talita and Stepien, Magdalena and Overvad, Kim and Tjonneland, Anne and Halkjaer, Jytte and Boutron-Ruault, Marie-Christine and Dossus, Laure and Racine, Antoine and Lagiou, Pagona and Bamia, Christina and Benetou, Vassiliki and Agnoli, Claudia and Palli, Domenico and Panico, Salvatore and Tumino, Rosario and Vineis, Paolo and Bueno-De-Mesquita, Bas and Peeters, Petra H. and Gram, Inger Torhild and Lund, Eiliv and Weiderpass, Elisabete and Quiros, J. Ramon and Agudo, Antonio and Sanchez, Maria-Jose and Gavrila, Diana and Barricarte, Aurelio and Dorronsoro, Miren and Ohlsson, Bodil and Lindkvist, Bjoern and Johansson, Anders and Sund, Malin and Khaw, Kay-Tee and Wareham, Nicholas and Travis, Ruth C. and Riboli, Elio and Pischon, Tobias},
  issn         = {1527-3350},
  language     = {eng},
  number       = {3},
  pages        = {858--871},
  publisher    = {John Wiley & Sons},
  series       = {Hepatology},
  title        = {Inflammatory and Metabolic Biomarkers and Risk of Liver and Biliary Tract Cancer},
  url          = {http://dx.doi.org/10.1002/hep.27016},
  volume       = {60},
  year         = {2014},
}