Elena De Mattia1, Erika Cecchin1, Jerry Polesel2, Francesco Lupo3, Claudio Tiribelli4,5, Marina Crovatto6, Angela Buonadonna7, Giuseppe Toffoli1. 1. Clinical and Experimental Pharmacology, CRO-National Cancer Institute, Aviano, PN, Italy. 2. Unit of Cancer Epidemiology, CRO-National Cancer Institute, Aviano, PN, Italy. 3. General Surgery 2U and Liver Transplantation Center, A.O.U. Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy. 4. Fondazione Italiana Fegato, AREA science Park, Trieste, Italy. 5. Department of Medical Sciences, University of Trieste, Trieste, Italy. 6. Cytogenetics and Molecular Biology Unit, Santa Maria degli Angeli Hospital, Pordenone, Italy. 7. Medical Oncology Unit, CRO-National Cancer Institute, Aviano, PN, Italy.
Abstract
BACKGROUND & AIMS: The definition of new biomarkers of hepatocellular carcinoma (HCC) risk, especially in high-risk HBV/HCV-positive population, is urgently needed to improve HCC clinical management. This study focused on variants of UDP-glucuronosyltransferase 1A (UGT1A) enzymes that catalyse the reaction of glucuronidation, one of the most important chemical defence pathway of the body. The aim of this study was to elucidate the contribution of UGT1A polymorphisms in predicting HCC susceptibility in Caucasians. METHODS: In this retrospective case-control analysis, 192 HCC liver transplanted patients represent the study group. Two age/sex-matched groups were used as control, one composed of 167 HBV- and/or HCV-infected individuals, and the other of 192 healthy subjects. All the cases were characterized for a panel of UGT1A1, UGT1A7 and UGT1A9 variants. The study end-point was the association between UGT1A markers and HCC onset. RESULTS: UGT1A7*3 allele emerged as a protective marker for HCC development among both high-risk HBV/HCV-positive patients (OR=0.64, P=.0026), and healthy subjects (OR=0.47, P=.0051). UGT1A1*28 (OR=0.61, P=.0013) and UGT1A9*22 (OR=2.18, P=.0003) alleles were also associated to HCC occurrence, especially among healthy subjects. UGT1A haplotype, summarizing the UGT1A genetic alterations, confirmed the protective role against HCC development emerged for low-activity alleles. The observed associations could probably be linked to an increase of serum levels of health-beneficial molecules including free bilirubin. CONCLUSION: A predictive effect of UGT1A polymorphisms on HCC risk was identified. If confirmed, these findings could contribute to improve the HCC surveillance, treatment tailoring and patients care.
BACKGROUND & AIMS: The definition of new biomarkers of hepatocellular carcinoma (HCC) risk, especially in high-risk HBV/HCV-positive population, is urgently needed to improve HCC clinical management. This study focused on variants of UDP-glucuronosyltransferase 1A (UGT1A) enzymes that catalyse the reaction of glucuronidation, one of the most important chemical defence pathway of the body. The aim of this study was to elucidate the contribution of UGT1A polymorphisms in predicting HCC susceptibility in Caucasians. METHODS: In this retrospective case-control analysis, 192 HCC liver transplanted patients represent the study group. Two age/sex-matched groups were used as control, one composed of 167 HBV- and/or HCV-infected individuals, and the other of 192 healthy subjects. All the cases were characterized for a panel of UGT1A1, UGT1A7 and UGT1A9 variants. The study end-point was the association between UGT1A markers and HCC onset. RESULTS:UGT1A7*3 allele emerged as a protective marker for HCC development among both high-risk HBV/HCV-positive patients (OR=0.64, P=.0026), and healthy subjects (OR=0.47, P=.0051). UGT1A1*28 (OR=0.61, P=.0013) and UGT1A9*22 (OR=2.18, P=.0003) alleles were also associated to HCC occurrence, especially among healthy subjects. UGT1A haplotype, summarizing the UGT1A genetic alterations, confirmed the protective role against HCC development emerged for low-activity alleles. The observed associations could probably be linked to an increase of serum levels of health-beneficial molecules including free bilirubin. CONCLUSION: A predictive effect of UGT1A polymorphisms on HCC risk was identified. If confirmed, these findings could contribute to improve the HCC surveillance, treatment tailoring and patients care.
Authors: Elena De Mattia; Erika Cecchin; Michela Guardascione; Luisa Foltran; Tania Di Raimo; Francesco Angelini; Mario D'Andrea; Giuseppe Toffoli Journal: World J Gastroenterol Date: 2019-08-07 Impact factor: 5.742
Authors: Silvia Mezzalira; Elena De Mattia; Michela Guardascione; Chiara Dalle Fratte; Erika Cecchin; Giuseppe Toffoli Journal: Int J Mol Sci Date: 2019-11-05 Impact factor: 5.923