TY - JOUR
T1 - Prospective association of liver function biomarkers with development of hepatobiliary cancers
AU - Stepien, Magdalena
AU - Fedirko, Veronika
AU - Duarte-Salles, Talita
AU - Ferrari, Pietro
AU - Freisling, Heinz
AU - Trepo, Elisabeth
AU - Trichopoulou, Antonia
AU - Bamia, Christina
AU - Weiderpass, Elisabete
AU - Olsen, Anja
AU - Tjønneland, Anne
AU - Overvad, Kim
AU - Boutron-Ruault, Marie Christine
AU - Fagherazzi, Guy
AU - Racine, Antoine
AU - Kühn, Tilman
AU - Kaaks, Rudolf
AU - Aleksandrova, Krasimira
AU - Boeing, Heiner
AU - Lagiou, Pagona
AU - Benetou, Vassiliki
AU - Trichopoulos, Dimitrios
AU - Palli, Domenico
AU - Grioni, Sara
AU - Tumino, Rosario
AU - Naccarati, Alessio
AU - Panico, Salvatore
AU - Bueno-de-Mesquita, H. Bas
AU - Peeters, Petra H.
AU - Lund, Eiliv
AU - Quirós, J. Ramón
AU - Nápoles, Osmel Companioni
AU - Sánchez, María José
AU - Dorronsoro, Miren
AU - Huerta, José María
AU - Ardanaz, Eva
AU - Ohlsson, Bodil
AU - Sjöberg, Klas
AU - Werner, Mårten
AU - Nystrom, Hanna
AU - Khaw, Kay Tee
AU - Key, Timothy J.
AU - Gunter, Marc
AU - Cross, Amanda
AU - Riboli, Elio
AU - Romieu, Isabelle
AU - Jenab, Mazda
N1 - Funding Information:
Financial support : This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA) (grant number 2009-139; PI: M. Jenab). The coordination of EPIC is financially supported by the European Commission (DG-SANCO); and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle Générale de l’Education Nationale; and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ); and Federal Ministry of Education and Research (Germany); Stavros Niarchos Foundation; Hellenic Health Foundation; and Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC); National Research Council; and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); and Statistics Netherlands (the Netherlands); European Research Council (ERC) (grant number ERC-2009-AdG 232997) and Nordforsk; and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS); Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra; and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology. (Spain); Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; and Wellcome Trust (UK).
Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - Biological markers
KW - Hepatobiliary cancer
KW - Liver function test
KW - Nested case-control study
KW - Prospective cohort
UR - http://www.scopus.com/inward/record.url?scp=84960091550&partnerID=8YFLogxK
U2 - 10.1016/j.canep.2016.01.002
DO - 10.1016/j.canep.2016.01.002
M3 - Article
C2 - 26773278
AN - SCOPUS:84960091550
SN - 1877-7821
VL - 40
SP - 179
EP - 187
JO - Cancer Epidemiology
JF - Cancer Epidemiology
ER -