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

Aleksandrova, Krasimira (author)
Boeing, Heiner (author)
Nöthlings, Ute (author)
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Jenab, Mazda (author)
Fedirko, Veronika (author)
Kaaks, Rudolf (author)
Lukanova-McGregor, Annekatrin (author)
Trichopoulou, Antonia (author)
Trichopoulos, Dimitrios (author)
Boffetta, Paolo (author)
Trepo, Elisabeth (author)
Westhpal, Sabine (author)
Duarte-Salles, Talita (author)
Stepien, Magdalena (author)
Overvad, Kim (author)
Tjønneland, Anne (author)
Halkjær, Jytte (author)
Boutron-Ruault, Marie-Christine (author)
Dossus, Laure (author)
Racine, Antoine (author)
Lagiou, Pagona (author)
Bamia, Christina (author)
Benetou, Vassiliki (author)
Agnoli, Claudia (author)
Palli, Domenico (author)
Panico, Salvatore (author)
Tumino, Rosario (author)
Vineis, Paolo (author)
Bueno-de-Mesquita, Bas (author)
Peeters, Petra H (author)
Gram, Inger Torhild (author)
Lund, Eiliv (author)
Weiderpass, Elisabete (author)
Quirós, J Ramón (author)
Agudo, Antonio (author)
Sánchez, María-José (author)
Gavrila, Diana (author)
Barricarte, Aurelio (author)
Dorronsoro, Miren (author)
Ohlsson, Bodil (author)
Lindkvist, Björn (author)
Johansson, Anders (author)
Sund, Malin 1972- (author)
Khaw, Kay-Tee (author)
Wareham, Nicholas (author)
Travis, Ruth C (author)
Riboli, Elio (author)
Pischon, Tobias (author)
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Wiley-Blackwell 2014
2014
English.
In: Hepatology. - 0270-9139. ; 60:3, 858-871
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Abstract Subject headings
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  • Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is 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), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). 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, 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 (CI-s) 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.

Subject headings

Medical and Health Sciences  (hsv)
Clinical Medicine  (hsv)
Cancer and Oncology  (hsv)
Medicin och hälsovetenskap  (hsv)
Klinisk medicin  (hsv)
Cancer och onkologi  (hsv)
Medical and Health Sciences  (hsv)
Clinical Medicine  (hsv)
Gastroenterology and Hepatology  (hsv)
Medicin och hälsovetenskap  (hsv)
Klinisk medicin  (hsv)
Gastroenterologi  (hsv)
medicin  (umu)
Medicine  (umu)

Keyword

liver cancer
biomarkers
hepatocellular carcinoma
bile duct cancer
inflammation
hyperinsulinemia

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