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Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case‐control study
Author(s) -
Fedirko Veronika,
DuarteSalles Talita,
Bamia Christina,
Trichopoulou Antonia,
Aleksandrova Krasimira,
Trichopoulos Dimitrios,
Trepo Elisabeth,
Tjønneland Anne,
Olsen Anja,
Overvad Kim,
BoutronRuault MarieChristine,
ClavelChapelon Françoise,
Kvaskoff Marina,
Kühn Tilman,
Lukanova Annie,
Boeing Heiner,
Buijsse Brian,
Klinaki Eleni,
Tsimakidi Chrysanthi,
Naccarati Alessio,
Tagliabue Giovanna,
Panico Salvatore,
Tumino Rosario,
Palli Domenico,
BuenodeMesquita H. Bas,
Siersema Peter D.,
Peters Petra H.,
Lund Eiliv,
Brustad Magritt,
Olsen Karina Standahl,
Weiderpass Elisabete,
ZamoraRos Raul,
Sánchez MaríaJosé,
Ardanaz Eva,
Amiano Pilar,
Navarro Carmen,
Quirós J. Ramón,
Werner Mårten,
Sund Malin,
Lindkvist Björn,
Malm Johan,
Travis Ruth C.,
Khaw KayTee,
Stepien Magdalena,
Scalbert Augustin,
Romieu Isabelle,
Lagiou Pagona,
Riboli Elio,
Jenab Mazda
Publication year - 2014
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.27079
Subject(s) - medicine , european prospective investigation into cancer and nutrition , prospective cohort study , hepatocellular carcinoma , vitamin d and neurology , odds ratio , confidence interval , gastroenterology , nested case control study , case control study , cohort study , logistic regression
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. (H epatology 2014;60:1222–1230)