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 5 138) 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 5 0.51, 95% confidence interval [CI], 0.26 to 0.99; P trend 5 0.04; per 10 nmol/L increase: IRR 5 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.

A D-vitamin metabolizmusa humán hepatocellularis carcinomában és az azt körülvevő tumormentes májszövetben

“…In vitro és in vivo vizsgálatok zajlanak a számos terápiás próbálkozás ellenére is igen rossz prognózisú hepatocellularis carcinoma carcinogenesisében betöltött szerepéről és esetleges terápiás alkalmazásáról [17,22,23]. Vita tárgyát képezi az alacsonyabb szérum-1,25-dihidroxi-D 3 -vitamin-szint és a hepatocellularis carcinoma kialakulásának magasabb kockázata között fennálló ösz-szefüggés [24,25]. Huang és munkacsoportja a közel-…”

The Significance of Vitamin D Receptor Gene Polymorphisms for Susceptibility to Hepatocellular Carcinoma in Subjects Infected with Hepatitis C Virus

“…An association has been established between low levels of vitamin D3 and several diseases including viral hepatitis and cancer development. Low serum levels of 25-OHD3 were proved to be associated with increased liver fibrosis in patients with non-alcoholic steatohepatitis [4] and type 2 diabetes mellitus [5] and reported to be associated with high risk of HCC development [6]. Moreover, the serum level of 25-OHD3 had been reported to affect the natural course and treatment response of chronic hepatitis C [7].…”

Nutrition and Hepatocellular Cancer

“…Results of the EPIC trial revealed that higher baseline levels of 25(OH)D are associated with a lower risk of HCC (per 10 nmol/l increase IRR 0.80; 95% CI 0.68-0.94) [48] . In contrast, dietary calcium, vitamin D, fat and protein from dairy sources are associated with increased HCC risk while the same nutrients from nondairy sources show inverse or null associations [49] .…”