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Lookup NU author(s): Nardeen Eldafashi, Dr Rebecca Darlay, Dr Ruchi ShuklaORCiD, Misti McCainORCiD, Robyn Watson, Dr Yang-Lin Liu, Nikki Mcstraw, Marco Youssef William Zaki, Professor Ann DalyORCiD, Joao Mauricio, Professor Alastair BurtORCiD, Professor Heather Cordell, Professor Quentin AnsteeORCiD, Professor Helen ReevesORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409; TM6SF2 rs58542926). Here, we have considered single-nucleotide polymorphisms (SNPs) in candidate immunoregulatory genes (MICA rs2596542; CD44 rs187115; PDCD1 rs7421861 and rs10204525), in 594 patients with NAFLD and 391 with NAFLD-HCC, from three European centres. Associations between age, body mass index, diabetes, cirrhosis and SNPs with HCC development were explored. PNPLA3 and TM6SF2 SNPs were associated with both progression to cirrhosis and NAFLD-HCC development, while PDCD1 SNPs were specifically associated with NAFLD-HCC risk, regardless of cirrhosis. PDCD1 rs7421861 was independently associated with NAFLD-HCC development, while PDCD1 rs10204525 acquired significance after adjusting for other risks, being most notable in the smaller numbers of women with NAFLD-HCC. The study highlights the potential impact of inter individual variation in immune tolerance induction in patients with NAFLD, both in the presence and absence of cirrhosis.
Author(s): Eldafashi N, Darlay R, Shukla R, McCain MV, Watson R, Liu YL, McStraw N, Fathy M, Fawzy MA, Zaki MYW, Daly AK, Mauricio JP, Burt AD, Haugk B, Cordell HJ, Bianco C, Dufour J-F, Valenti L, Anstee QM, Reeves HL
Publication type: Article
Publication status: Published
Journal: Cancers
Year: 2021
Volume: 13
Issue: 6
Online publication date: 19/03/2021
Acceptance date: 16/03/2021
Date deposited: 29/03/2021
ISSN (electronic): 2072-6694
Publisher: MDPI AG
URL: https://doi.org/10.3390/cancers13061412
DOI: 10.3390/cancers13061412
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