title: Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study.
abstract: 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; Ptrend  = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta GA, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.forename: Talita
authors.initials: T
authors.lastname: Duarte-Salles
authors.forename: Christina
authors.initials: C
authors.lastname: Bamia
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Trepo
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Marina
authors.initials: M
authors.lastname: Kvaskoff
authors.forename: Tilman
authors.initials: T
authors.lastname: Kühn
authors.forename: Annie
authors.initials: A
authors.lastname: Lukanova
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Brian
authors.initials: B
authors.lastname: Buijsse
authors.forename: Eleni
authors.initials: E
authors.lastname: Klinaki
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Tsimakidi
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tagliabue
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peters
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Magritt
authors.initials: M
authors.lastname: Brustad
authors.forename: Karina Standahl
authors.initials: KS
authors.lastname: Olsen
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.forename: Raul
authors.initials: R
authors.lastname: Zamora-Ros
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.forename: Mårten
authors.initials: M
authors.lastname: Werner
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.forename: Björn
authors.initials: B
authors.lastname: Lindkvist
authors.forename: Johan
authors.initials: J
authors.lastname: Malm
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stepien
authors.forename: Augustin
authors.initials: A
authors.lastname: Scalbert
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D014807:Vitamin D / Q000097:blood*
chemical_list: D015415:Biomarkers; D014807:Vitamin D