Cancer Chemotherapy and Pharmacology (2018) 81:615–620
Vitamin D pathway gene polymorphisms and hepatocellular
carcinoma in chronic hepatitis C-aﬀected patients treated with new
· Lucio Boglione
· Amedeo De Nicolò
· Fabio Favata
· Alessandra Ariaudo
Simone Mornese Pinna
· Federica Guido
· Valeria Avataneo
· Marco Cantù
· Chiara Carcieri
· Giuseppe Cariti
Giovanni Di Perri
· Antonio D’Avolio
Received: 24 October 2017 / Accepted: 10 January 2018 / Published online: 22 January 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Purpose Since HCV infection may lead to hepatocellular carcinoma (HCC) and vitamin D (deﬁciency) is related to cancer,
we investigated if SNPs in genes involved in vitamin D pathway could predict HCV-related HCC presence in patients treated
with new anti-HCV drugs.
Methods Patients with chronic hepatitis C and treated with direct-acting antivirals were enrolled. SNPs in VDR, CYP27B1,
CYP24A1 and GC genes were assessed through real-time PCR. 258 patients were analyzed.
Results HCC was present in six patients, all taking sofosbuvir, all males and ﬁve/six had cirrhosis. HCV-RNA log levels
at baseline were statistically diﬀerent between patients with and without HCC. VDR FokI T > C SNP resulted associated
with HCC: all the CC patients were free from HCC. An association between HCC presence and undetectable HCV-RNA
at 1 month of therapy was suggested; cirrhosis was related to HCC. HCC risk factors were age, ribavirin administration,
IL28Brs12979860CC and previous treatments; VDR FokICC, sex and insulin resistance were protective factors.
Conclusions These data highlighted vitamin D pathway gene SNPs and HCC relationship in the Italian population; further
studies are required.
Keywords Viral hepatitis · Hepatocellular carcinoma · Vitamin D · VDR · Pharmacogenetics · SNP · Sofosbuvir
Dual therapy (ribavirin, RBV and pegylated-interferon) has
been considered the standard of care for chronic hepatitis C
(CHC) treatment in the last 20 years.
To date, new more eﬀective direct-acting antiviral drugs
(DAAs), with pan-genotypic activity and increased tolerabil-
ity, enhanced the probability to achieve sustained virological
response (SVR, nearly 100%) .
Hepatitis C virus (HCV) infection is one of the major
public health problems worldwide, leading to several clinical
consequences, including hepatocellular carcinoma (HCC)
Although the relationship between HCV and the HCC
development is well demonstrated, pathogenetic mechanism
involved in hepatocarcinogenesis remains unclear; infact it
is a complex and multi-factorial process, regulated by both
environmental and genetic features . Particularly, the
role of polymorphisms in genes encoding inﬂammatory
Jessica Cusato and Lucio Boglione equally contributed to this
*UNI EN ISO 9001:2008 and 13485:2012 Certiﬁed (PHASE I)
**Certiﬁcation for: “Design, Development and Application
of Determination Methods for Clinical Analytes and Drugs.
Pharmacogenetic Analyses” and “Design and Production of
Diagnostic Medical Devices In Vitro”.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00280-018-3520-0) contains
supplementary material, which is available to authorized users.
* Jessica Cusato
Department of Medical Sciences, Amedeo di Savoia
Hospital, University of Turin, Turin, Italy
Laboratory of Clinical Biochemistry and Pharmacology,
Department of Laboratory Medicine EOLAB, Ente
Ospedaliero Cantonale, Bellinzona, Switzerland