Prospective association of liver function biomarkers with development of hepatobiliary cancers

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Title: Prospective association of liver function biomarkers with development of hepatobiliary cancers
Authors: Stepien, M
Fedirko, V
Duarte-Salles, T
Ferrari, P
Freisling, H
Trepo, E
Trichopoulou, A
Bamia, C
Weiderpass, E
Olsen, A
Tjonneland, A
Overvad, K
Boutron-Ruault, M-C
Fagherazzi, G
Racine, A
Kuehn, T
Kaaks, R
Aleksandrova, K
Boeing, H
Lagiou, P
Benetou, V
Trichopoulos, D
Palli, D
Grioni, S
Tumino, R
Naccarati, A
Panico, S
Bueno-de-Mesquita, HB
Peeters, PH
Lund, E
Quiros, JR
Napoles, OC
Sanchez, M-J
Dorronsoro, M
Maria Huerta, J
Ardanaz, E
Ohlsson, B
Sjoberg, K
Werner, M
Nystrom, H
Khaw, K-T
Key, TJ
Gunter, M
Cross, A
Riboli, E
Romieu, I
Jenab, M
Item Type: Journal Article
Abstract: Introduction Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers. Methods A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI). Results In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT) = 4.23, 95%CI:2.72–6.59; OR(ALP) = 3.43, 95%CI:2.31–5.10;OR(AST) = 3.00, 95%CI:2.04-4.42; OR(ALT) = 2.69, 95%CI:1.89–3.84; OR(Bilirubin) = 2.25, 95%CI:1.58–3.20). Each liver enzyme (OR(GGT) = 4.98; 95%CI:1.75–14.17; OR(AST) = 3.10, 95%CI:1.04–9.30; OR(ALT) = 2.86, 95%CI:1.26–6.48, OR(ALP) = 2.31, 95%CI:1.10–4.86) but not bilirubin (OR(Bilirubin) = 1.46,95%CI:0.85–2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP) = 1.59, 95%CI:1.20–2.09). Conclusion This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.
Issue Date: 11-Jan-2016
Date of Acceptance: 4-Jan-2016
ISSN: 1877-7821
Publisher: Elsevier
Start Page: 179
End Page: 187
Journal / Book Title: Cancer Epidemiology
Volume: 40
Copyright Statement: © 2016, Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Sponsor/Funder: University Medical Center Utrecht
Imperial College Trust
Funder's Grant Number: N/A
Keywords: Science & Technology
Life Sciences & Biomedicine
Public, Environmental & Occupational Health
Hepatobiliary cancer
Liver function test
Biological markers
Prospective cohort
Nested case-control study
Aged, 80 and over
Alanine Transaminase
Alkaline Phosphatase
Aspartate Aminotransferases
Bile Duct Neoplasms
Biliary Tract Neoplasms
Carcinoma, Hepatocellular
Case-Control Studies
Liver Function Tests
Liver Neoplasms
Middle Aged
Prospective Studies
Risk Factors
Young Adult
1112 Oncology And Carcinogenesis
1117 Public Health And Health Services
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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