Prediagnostic Circulating Vitamin D Levels and Risk of Hepatocellular Carcinoma in European Populations: A Nested Case-Control Study

Veronika Fedirko, Talita Duarte-Salles, Christina Bamia, Antonia Trichopoulou, Krasimira Aleksandrova, Dimitrios Trichopoulos, Elisabeth Trepo, Anne Tjonneland, Anja Olsen, Kim Overvad, Marie-Christine Boutron-Ruault, Francoise Clavel-Chapelon, Marina Kvaskoff, Tilman Kuehn, Annie Lukanova, Heiner Boeing, Brian Buijsse, Eleni Klinaki, Chrysanthi Tsimakidi, Alessio NaccaratiGiovanna Tagliabue, Salvatore Panico, Rosario Tumino, Domenico Palli, H. Bas Bueno-de-Mesquita, Peter D. Siersema, Petra H. Peters, Eiliv Lund, Magritt Brustad, Karina Standahl Olsen, Elisabete Weiderpass, Raul Zamora-Ros, Maria-Jose Sanchez, Eva Ardanaz, Pilar Amiano, Carmen Navarro, J. Ramon Quiros, Marten Werner, Malin Sund, Bjorn Lindkvist, Johan Malm, Ruth C. Travis, Kay-Tee Khaw, Magdalena Stepien, Augustin Scalbert, Isabelle Romieu, Pagona Lagiou, Elio Riboli, Mazda Jenab

Research output: Contribution to journalArticlepeer-review


The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; P-trend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;60:1222-1230)
Original languageEnglish
Pages (from-to)1222-1230
Issue number4
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Gastroenterology and Hepatology


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