{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:14:21Z","timestamp":1767917661179,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The positive relationships of non\u2010alcoholic fatty liver disease (NAFLD) and cirrhosis with liver cancer were shown in previous observational studies, while further Mendelian randomization (MR) investigations are needed to confirm the possible causal associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aimed to explore whether NAFLD and cirrhosis were causally related to liver cancer using MR in European and East Asian populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>For European populations, NAFLD data were obtained from a genome\u2010wide meta\u2010analysis (8434 patients and 770\u2009180 controls). The data on chronic elevation of alanine aminotransferase (cALT), a proxy of NAFLD, were derived from Million Veteran Program (68\u2009725 patients and 95\u2009472 controls). Cirrhosis data were collected from two sources: a genome\u2010wide association study of five cohorts (4829 patients and 72\u2009705 controls) and FinnGen (1931 patients and 216\u2009861 controls). Liver cancer data were collected from FinnGen (304 patients and 174\u2009006 controls). For East Asian populations, the data on cirrhosis (2184 patients and 210\u2009269 controls) and hepatocellular carcinoma (1866 patients and 195\u2009745 controls) were obtained from Biobank Japan.<\/jats:p><jats:p>Three, 41, seven, six, and three single\u2010nucleotide polymorphisms were used for NAFLD (European), cALT (European), cirrhosis (European\u2010five cohorts), cirrhosis (European\u2010FinnGen), and cirrhosis (East Asian), respectively. We used inverse\u2010variance weighted as the primary method to calculate the odds ratio (OR) and 95% confidence interval (CI).<\/jats:p><jats:p>Among European populations, genetically\u2010predicted NAFLD, cALT, cirrhosis (five cohorts), and cirrhosis (FinnGen) were positively associated with liver cancer, with ORs (95% CIs) of 6.62 (3.81\u201311.50) (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), 2.59 (1.70\u20133.94) (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), 3.38 (2.41\u20134.75) (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), and 2.62 (1.20\u20135.72) (<jats:italic>p<\/jats:italic>\u2009=\u2009.015). Among East Asian populations, there was also a positive association between genetically\u2010predicted cirrhosis and hepatocellular carcinoma (OR\u2009=\u20092.12; 95% CI\u2009=\u20091.78\u20132.52; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study utilized MR to complementarily confirm the positive connections of NAFLD and cirrhosis with liver cancer, as identified in earlier observational research. Subsequent MR investigations involving more liver cancer cases are needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.1913","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T07:16:37Z","timestamp":1697440597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Associations of non\u2010alcoholic fatty liver disease and cirrhosis with liver cancer in European and East Asian populations: A Mendelian randomization study"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4848-2953","authenticated-orcid":false,"given":"Yunyang","family":"Deng","sequence":"first","affiliation":[{"name":"The Jockey Club School of Public Health and Primary Care, Faculty of Medicine The Chinese University of Hong Kong  Hong Kong SAR 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