Журнал канцерогенеза и мутагенеза

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Polygenic Risk Score in NAFLD/NASH-Associated Hepatocellular Carcinoma Along With Multifactorial Process

Kazumi Fujioka

The prevalence and incidence of Non-Alcoholic Fatty Liver Disease (NAFLD) is increasing due to the epidemics of obesity and Type 2 Diabetes Mellitus (T2DM). Recently, a link between NAFLD and hypertension along with new genetic expression has been identified. NAFLD is a multisystem disease and is associated with hepatic and extrahepatic diseases. The author previously described that in addition to the epidemiological and single genetic factors, the study of combined effect of the variants may be attributed to the risk stratification in NAFLD/NASHrelated hepatocellular carcinoma (HCC) and also suggested that the stratification of the risk of NAFLD related HCC especially non-cirrhotic HCC based on the characteristic clinical and genetic evidence may contribute to the prevention, prediction, and surveillance. The risk factors and multifactorial process include obesity, T2DM, hypertension, ethnicity, genetic Polymorphism PNPLA3, TM6SF2, GCKR, MBOA17, and HSD17B13, epigenetic factors, transcriptional factors, post-transcriptional modification, and hepatic lipogenesis carcinogenesis in NAFLD. In this article, the author reviewed the current knowledge of risk factors, multifactorial process, and polygenic risk score (PRS) in NAFLD-related HCC. Although several risk factors and complex and multifactorial process are present in the progression of NAFLD-related HCC, the author suggests that comprehensive determination using epidemiological factor and PRS including PNPLA3, TM6SF2, GCKR, MBOAT7, and HSD17B13 may be attributed to the risk stratification, prognosis, and therapeutic strategy in cirrhosis and non-cirrhosis patients with NAFLDrelated HCC.