Edmondo Falleti1, Annarosa Cussigh1, Sara Cmet1, Carlo Fabris1, Pierluigi Toniutto2. 1. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Italy. 2. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Italy. Electronic address: pierluigi.toniutto@uniud.it.
Abstract
BACKGROUND: PNPLA3 rs738409 polymorphism is associated with fatty liver disease, alcoholic or non-alcoholic (NAFLD) and hepatocellular carcinoma (HCC). TM6SF2 rs58542926 is clearly associated with NAFLD, but it is not clearly associated with HCC. The relationship between TM6SF2 rs58542926 and HCC and the potential synergistic effect of TM6SF2 and PNPLA3 variants in modifying the risk of HCC are not known. AIM: This study assessed the interaction between PNPLA3 rs738409 and TM6SF2 rs58542926 variants in the conditioning of HCC development. METHODS: A total of 511 cirrhotic patients (44% alcohol-related, 56% viral, 57.5% liver transplanted) were retrospectively investigated for HCC occurrence. PNPLA3 rs734809 and TM6SF2 rs58542926 were genotyped using restriction fragment length polymorphism and real-time allelic discrimination polymerase chain reaction methods. RESULTS: Patients with HCC were more likely to be PNPLA3 rs734809 G/G homozygotes (41/150 vs. 60/361, p=0.009) or TM6SF2 rs58542926 C/T-T/T (27/150 vs. 41/361, p=0.044). The presence of either PNPLA3 G/G or TM6SF2*/T identified high-risk genotypes for HCC, which were strongly associated with HCC (64/150 vs. 93/361, p=0.0002). This association was evident in alcohol-related (p=0.0007) but not in viral cirrhosis. CONCLUSION: TM6SF2 C/T or T/T in conjunction with PNPLA3 G/G variants may be potential genetic risk factors for developing HCC in alcohol-related cirrhosis.
BACKGROUND:PNPLA3rs738409 polymorphism is associated with fatty liver disease, alcoholic or non-alcoholic (NAFLD) and hepatocellular carcinoma (HCC). TM6SF2rs58542926 is clearly associated with NAFLD, but it is not clearly associated with HCC. The relationship between TM6SF2rs58542926 and HCC and the potential synergistic effect of TM6SF2 and PNPLA3 variants in modifying the risk of HCC are not known. AIM: This study assessed the interaction between PNPLA3rs738409 and TM6SF2rs58542926 variants in the conditioning of HCC development. METHODS: A total of 511 cirrhotic patients (44% alcohol-related, 56% viral, 57.5% liver transplanted) were retrospectively investigated for HCC occurrence. PNPLA3rs734809 and TM6SF2rs58542926 were genotyped using restriction fragment length polymorphism and real-time allelic discrimination polymerase chain reaction methods. RESULTS:Patients with HCC were more likely to be PNPLA3rs734809 G/G homozygotes (41/150 vs. 60/361, p=0.009) or TM6SF2rs58542926 C/T-T/T (27/150 vs. 41/361, p=0.044). The presence of either PNPLA3 G/G or TM6SF2*/T identified high-risk genotypes for HCC, which were strongly associated with HCC (64/150 vs. 93/361, p=0.0002). This association was evident in alcohol-related (p=0.0007) but not in viral cirrhosis. CONCLUSION:TM6SF2 C/T or T/T in conjunction with PNPLA3 G/G variants may be potential genetic risk factors for developing HCC in alcohol-related cirrhosis.
Authors: Nicole Ehrhardt; Michael E Doche; Shuang Chen; Hui Z Mao; Meghan T Walsh; Candy Bedoya; Maha Guindi; Weidong Xiong; Joseph Ignatius Irudayam; Jahangir Iqbal; Sebastien Fuchs; Samuel W French; M Mahmood Hussain; Moshe Arditi; Vaithilingaraja Arumugaswami; Miklós Péterfy Journal: Hum Mol Genet Date: 2017-07-15 Impact factor: 5.121
Authors: Pierluigi Ramadori; Francisco Javier Cubero; Christian Liedtke; Christian Trautwein; Yulia A Nevzorova Journal: Cancers (Basel) Date: 2017-09-25 Impact factor: 6.639