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Erschienen in: Cancer Chemotherapy and Pharmacology 3/2018

22.01.2018 | Short Communication

Vitamin D pathway gene polymorphisms and hepatocellular carcinoma in chronic hepatitis C-affected patients treated with new drugs

verfasst von: Jessica Cusato, 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

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2018

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Abstract

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.
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Literatur
1.
Zurück zum Zitat Gonzalez-Grande R, Jimenez-Perez M, Gonzalez Arjona C, Mostazo Torres J (2016) New approaches in the treatment of hepatitis C. World J Gastroenterol 22:1421–1432CrossRefPubMedPubMedCentral Gonzalez-Grande R, Jimenez-Perez M, Gonzalez Arjona C, Mostazo Torres J (2016) New approaches in the treatment of hepatitis C. World J Gastroenterol 22:1421–1432CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Alter MJ (1997) The epidemiology of acute and chronic hepatitis C. Clin Liver Dis 1:559–568, vi–viiCrossRef Alter MJ (1997) The epidemiology of acute and chronic hepatitis C. Clin Liver Dis 1:559–568, vi–viiCrossRef
3.
Zurück zum Zitat Massard J, Ratziu V, Thabut D, Moussalli J, Lebray P, Benhamou Y, Poynard T (2006) Natural history and predictors of disease severity in chronic hepatitis C. J Hepatol 44:S19–S24CrossRefPubMed Massard J, Ratziu V, Thabut D, Moussalli J, Lebray P, Benhamou Y, Poynard T (2006) Natural history and predictors of disease severity in chronic hepatitis C. J Hepatol 44:S19–S24CrossRefPubMed
4.
Zurück zum Zitat Falleti E, Bitetto D, Fabris C, Cussigh A, Fontanini E, Fornasiere E, Fumolo E, Bignulin S, Cmet S, Minisini R, Pirisi M, Toniutto P (2010) Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis. World J Gastroenterol 16:3016–3024CrossRefPubMedPubMedCentral Falleti E, Bitetto D, Fabris C, Cussigh A, Fontanini E, Fornasiere E, Fumolo E, Bignulin S, Cmet S, Minisini R, Pirisi M, Toniutto P (2010) Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis. World J Gastroenterol 16:3016–3024CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Lange CM, Miki D, Ochi H, Nischalke HD, Bojunga J, Bibert S, Morikawa K, Gouttenoire J, Cerny A, Dufour JF, Gorgievski-Hrisoho M, Heim MH, Malinverni R, Mullhaupt B, Negro F, Semela D, Kutalik Z, Muller T, Spengler U, Berg T, Chayama K, Moradpour D, Bochud PY (2013) Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development. PLoS One 8:e64053CrossRefPubMedPubMedCentral Lange CM, Miki D, Ochi H, Nischalke HD, Bojunga J, Bibert S, Morikawa K, Gouttenoire J, Cerny A, Dufour JF, Gorgievski-Hrisoho M, Heim MH, Malinverni R, Mullhaupt B, Negro F, Semela D, Kutalik Z, Muller T, Spengler U, Berg T, Chayama K, Moradpour D, Bochud PY (2013) Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development. PLoS One 8:e64053CrossRefPubMedPubMedCentral
6.
7.
Zurück zum Zitat Kostner K, Denzer N, Muller CS, Klein R, Tilgen W, Reichrath J (2009) The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer Res 29:3511–3536PubMed Kostner K, Denzer N, Muller CS, Klein R, Tilgen W, Reichrath J (2009) The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer Res 29:3511–3536PubMed
8.
Zurück zum Zitat Rai V, Abdo J, Agrawal S, Agrawal DK (2017) Vitamin D receptor polymorphism and cancer: an update. Anticancer Res 37:3991–4003PubMed Rai V, Abdo J, Agrawal S, Agrawal DK (2017) Vitamin D receptor polymorphism and cancer: an update. Anticancer Res 37:3991–4003PubMed
9.
Zurück zum Zitat Peng Q, Yang S, Lao X, Li R, Chen Z, Wang J, Qin X, Li S (2014) Association of single nucleotide polymorphisms in VDR and DBP genes with HBV-related hepatocellular carcinoma risk in a Chinese population. PLoS One 9:e116026CrossRefPubMedPubMedCentral Peng Q, Yang S, Lao X, Li R, Chen Z, Wang J, Qin X, Li S (2014) Association of single nucleotide polymorphisms in VDR and DBP genes with HBV-related hepatocellular carcinoma risk in a Chinese population. PLoS One 9:e116026CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Yao X, Zeng H, Zhang G, Zhou W, Yan Q, Dai L, Wang X (2013) The associated ion between the VDR gene polymorphisms and susceptibility to hepatocellular carcinoma and the clinicopathological features in subjects infected with HBV. Biomed Res Int 2013:953–974 Yao X, Zeng H, Zhang G, Zhou W, Yan Q, Dai L, Wang X (2013) The associated ion between the VDR gene polymorphisms and susceptibility to hepatocellular carcinoma and the clinicopathological features in subjects infected with HBV. Biomed Res Int 2013:953–974
11.
Zurück zum Zitat Hung CH, Chiu YC, Hu TH, Chen CH, Lu SN, Huang CM, Wang JH, Lee CM (2014) Significance of vitamin d receptor gene polymorphisms for risk of hepatocellular carcinoma in chronic hepatitis C. Transl Oncol 7:503–507CrossRefPubMedPubMedCentral Hung CH, Chiu YC, Hu TH, Chen CH, Lu SN, Huang CM, Wang JH, Lee CM (2014) Significance of vitamin d receptor gene polymorphisms for risk of hepatocellular carcinoma in chronic hepatitis C. Transl Oncol 7:503–507CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Nada HA, Elsamanoudy AZ, Elalfy HA, Mogahed RE (2016) Study of vitamin D receptor-FOK-I gene polymorphism in chronic hepatitis C induced hepatocellular carcinoma patients: a case control study. Int J Innov Res Sci Eng Technol 5:4645–4655 Nada HA, Elsamanoudy AZ, Elalfy HA, Mogahed RE (2016) Study of vitamin D receptor-FOK-I gene polymorphism in chronic hepatitis C induced hepatocellular carcinoma patients: a case control study. Int J Innov Res Sci Eng Technol 5:4645–4655
13.
Zurück zum Zitat Poon AH, Gong L, Brasch-Andersen C, Litonjua AA, Raby BA, Hamid Q, Laprise C, Weiss ST, Altman RB, Klein TE (2012) Very important pharmacogene summary for VDR. Pharmacogenet Genom 22:758–763CrossRef Poon AH, Gong L, Brasch-Andersen C, Litonjua AA, Raby BA, Hamid Q, Laprise C, Weiss ST, Altman RB, Klein TE (2012) Very important pharmacogene summary for VDR. Pharmacogenet Genom 22:758–763CrossRef
14.
Zurück zum Zitat Cusato J, Boglione L, De Nicolo A, Cardellino CS, Carcieri C, Cariti G, Di Perri G, D’Avolio A (2016) Vitamin D pathway gene polymorphisms as predictors of hepatitis C virus-related mixed cryoglobulinemia. Pharmacogenet Genom 26:307–310CrossRef Cusato J, Boglione L, De Nicolo A, Cardellino CS, Carcieri C, Cariti G, Di Perri G, D’Avolio A (2016) Vitamin D pathway gene polymorphisms as predictors of hepatitis C virus-related mixed cryoglobulinemia. Pharmacogenet Genom 26:307–310CrossRef
15.
Zurück zum Zitat D’Avolio A, Cusato J, De Nicolo A, Allegra S, Di Perri G (2016) Pharmacogenetics of ribavirin-induced anemia in HCV patients. Pharmacogenomics 17:925–941 D’Avolio A, Cusato J, De Nicolo A, Allegra S, Di Perri G (2016) Pharmacogenetics of ribavirin-induced anemia in HCV patients. Pharmacogenomics 17:925–941
16.
Zurück zum Zitat Cusato J, Allegra S, Boglione L, De Nicolo A, Baietto L, Cariti G, Di Perri G, D’Avolio A (2014) Vitamin D pathway gene variants and HCV-2/3 therapy outcomes. Antivir Ther 20:335–341CrossRef Cusato J, Allegra S, Boglione L, De Nicolo A, Baietto L, Cariti G, Di Perri G, D’Avolio A (2014) Vitamin D pathway gene variants and HCV-2/3 therapy outcomes. Antivir Ther 20:335–341CrossRef
17.
Zurück zum Zitat D’Avolio A, Ciancio A, Siccardi M, Baietto L, Simiele M, Cariti G, Calcagno A, Smedile A, Cusato J, Bonora S, Rizzetto M, Di Perri G (2011) Ribavirin pharmacokinetics and interleukin 28B plus cytochrome P450 27B1 single-nucleotide polymorphisms as predictors of response to pegylated interferon/ribavirin treatment in patients infected with hepatitis C virus genotype 1/4. Hepatology 54:2278–2279CrossRefPubMed D’Avolio A, Ciancio A, Siccardi M, Baietto L, Simiele M, Cariti G, Calcagno A, Smedile A, Cusato J, Bonora S, Rizzetto M, Di Perri G (2011) Ribavirin pharmacokinetics and interleukin 28B plus cytochrome P450 27B1 single-nucleotide polymorphisms as predictors of response to pegylated interferon/ribavirin treatment in patients infected with hepatitis C virus genotype 1/4. Hepatology 54:2278–2279CrossRefPubMed
18.
Zurück zum Zitat D’Avolio A, Ciancio A, Siccardi M, Smedile A, Simiele M, Cusato J, Baietto L, Aguilar Marucco D, Cariti G, Calcagno A, Gonzalez de Requena D, Sciandra M, Troshina G, Caviglia GP, Bonora S, Rizzetto M, Di Perri G (2012) Negative predictive value of IL28B, SLC28A2, and CYP27B1 SNPs and low RBV plasma exposure for therapeutic response to PEG/IFN-RBV treatment. Ther Drug Monit 34:722–728CrossRefPubMed D’Avolio A, Ciancio A, Siccardi M, Smedile A, Simiele M, Cusato J, Baietto L, Aguilar Marucco D, Cariti G, Calcagno A, Gonzalez de Requena D, Sciandra M, Troshina G, Caviglia GP, Bonora S, Rizzetto M, Di Perri G (2012) Negative predictive value of IL28B, SLC28A2, and CYP27B1 SNPs and low RBV plasma exposure for therapeutic response to PEG/IFN-RBV treatment. Ther Drug Monit 34:722–728CrossRefPubMed
19.
Zurück zum Zitat Cusato J, De Nicolo A, Boglione L, Favata F, Ariaudo A, Mornese Pinna S, Guido F, Avataneo V, Carcieri C, Cariti G, Di Perri G, D’Avolio A (2017) Influence of ABCB11 and HNF4alpha genes on daclatasvir plasma concentration: preliminary pharmacogenetic data from the Kineti-C study. J Antimicrob Chemother 72:2846–2849CrossRefPubMed Cusato J, De Nicolo A, Boglione L, Favata F, Ariaudo A, Mornese Pinna S, Guido F, Avataneo V, Carcieri C, Cariti G, Di Perri G, D’Avolio A (2017) Influence of ABCB11 and HNF4alpha genes on daclatasvir plasma concentration: preliminary pharmacogenetic data from the Kineti-C study. J Antimicrob Chemother 72:2846–2849CrossRefPubMed
20.
Zurück zum Zitat Morio K, Imamura M, Kawakami Y, Morio R, Hatooka M, Kan H, Fujino H, Fukuhara T, Kobayashi T, Masaki K, Ono A, Nakahara T, Urabe A, Yokoyama S, Nagaoki Y, Kawaoka T, Hiraga N, Tsuge M, Hiramatsu A, Hayes CN, Aikata H, Ochi H, Chayama K (2016) Effects of ITPA polymorphism on decrease of hemoglobin during simeprevir, peg-interferon, and ribavirin combination treatment for chronic hepatitis C. Hepatol Res 46:1256–1263CrossRefPubMed Morio K, Imamura M, Kawakami Y, Morio R, Hatooka M, Kan H, Fujino H, Fukuhara T, Kobayashi T, Masaki K, Ono A, Nakahara T, Urabe A, Yokoyama S, Nagaoki Y, Kawaoka T, Hiraga N, Tsuge M, Hiramatsu A, Hayes CN, Aikata H, Ochi H, Chayama K (2016) Effects of ITPA polymorphism on decrease of hemoglobin during simeprevir, peg-interferon, and ribavirin combination treatment for chronic hepatitis C. Hepatol Res 46:1256–1263CrossRefPubMed
21.
Zurück zum Zitat Morio K, Imamura M, Kawakami Y, Nakahara T, Nagaoki Y, Kawaoka T, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Makokha GN, Ochi H, Amano H, Arataki K, Moriya T, Ito H, Tsuji K, Kohno H, Waki K, Tamura T, Nakamura T, Chayama K (2016) ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C. J Gastroenterol 52:746–753CrossRefPubMed Morio K, Imamura M, Kawakami Y, Nakahara T, Nagaoki Y, Kawaoka T, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Makokha GN, Ochi H, Amano H, Arataki K, Moriya T, Ito H, Tsuji K, Kohno H, Waki K, Tamura T, Nakamura T, Chayama K (2016) ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C. J Gastroenterol 52:746–753CrossRefPubMed
Metadaten
Titel
Vitamin D pathway gene polymorphisms and hepatocellular carcinoma in chronic hepatitis C-affected patients treated with new drugs
verfasst von
Jessica Cusato
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
Publikationsdatum
22.01.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 3/2018
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3520-0

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