Prospective association of liver function biomarkers with development of hepatobiliary cancers

Magdalena Stepien, Veronika Fedirko, Talita Duarte-Salles, Pietro Ferrari, Heinz Freisling, Elisabeth Trepo, Antonia Trichopoulou, Christina Bamia, Elisabete Weiderpass, Anja Olsen, Anne Tjønneland, Kim Overvad, Marie Christine Boutron-Ruault, Guy Fagherazzi, Antoine Racine, Tilman Kühn, Rudolf Kaaks, Krasimira Aleksandrova, Heiner Boeing, Pagona LagiouVassiliki Benetou, Dimitrios Trichopoulos, Domenico Palli, Sara Grioni, Rosario Tumino, Alessio Naccarati, Salvatore Panico, H. Bas Bueno-de-Mesquita, Petra H. Peeters, Eiliv Lund, J. Ramón Quirós, Osmel Companioni Nápoles, María José Sánchez, Miren Dorronsoro, José María Huerta, Eva Ardanaz, Bodil Ohlsson, Klas Sjöberg, Mårten Werner, Hanna Nystrom, Kay Tee Khaw, Timothy J. Key, Marc Gunter, Amanda Cross, Elio Riboli, Isabelle Romieu, Mazda Jenab*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalCancer Epidemiology
Publication statusPublished - 1 Feb 2016
Externally publishedYes


  • Biological markers
  • Hepatobiliary cancer
  • Liver function test
  • Nested case-control study
  • Prospective cohort


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