期刊
HEPATOLOGY
卷 60, 期 3, 页码 858-871出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1002/hep.27016
关键词
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资金
- Federal Ministry of Education and Research
- German Research Foundation
- German Research Foundation (Germany) [PI 419/3-1]
- French National Cancer Institute (L'Institut National du Cancer
- INCA) [2009-139]
- European Commission (DG-SANCO)
- International Agency for Research on Cancer
- Danish Cancer Society (Denmark)
- Ligue Contre le Cancer
- Institut Gustave Roussy
- Mutuelle Generale de l'Education Nationale
- Institut National de la Sante et de la Recherche Medicale (INSERM
- France)
- Deutsche Krebshilfe
- Deutsches Krebsforschungszentrum
- Hellenic Health Foundation
- Stavros Niarchos Foundation
- Hellenic Ministry of Health and Social Solidarity (Greece)
- Italian Association for Research on Cancer (AIRC)
- National Research Council
- AIRE-ONLUS Ragusa
- AVIS Ragusa, Sicilian Government (Italy)
- Dutch Ministry of Public Health, Welfare and Sports
- Netherlands Cancer Registry
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands (the Netherlands)
- European Research Council (ERC) [ERC-2009-AdG 232997]
- Nordforsk
- Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway)
- Health Research Fund
- Regional Government of Andalucia [6236]
- Regional Government of Asturias [6236]
- Regional Government of Basque Country [6236]
- Regional Government of Murcia [6236]
- Regional Government of Navarra [6236]
- ISCIII RETIC (Spain) [RD06/0020]
- Swedish Cancer Society
- Swedish Scientific Council
- Regional Government of Skane
- Vasterbotten (Sweden)
- Cancer Research UK
- Medical Research Council
- Stroke Association
- British Heart Foundation
- Department of Health
- Food Standards Agency
- Wellcome Trust (UK)
- MRC [MC_UU_12015/1] Funding Source: UKRI
- Cancer Research UK [14136, 16491] Funding Source: researchfish
- Medical Research Council [G1000143, MC_U106179471, MC_UU_12015/1, G0401527] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10114, NF-SI-0512-10135] Funding Source: researchfish
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.
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