{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:11:39Z","timestamp":1788307899927,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST111\u20102629\u2010B\u2010182\u2010001\u2010;MOST111\u20102314\u2010B\u2010182A\u2010156\u2010"],"award-info":[{"award-number":["MOST111\u20102629\u2010B\u2010182\u2010001\u2010;MOST111\u20102314\u2010B\u2010182A\u2010156\u2010"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The impacts of patatin\u2010like phospholipase domain\u2010containing protein 3 (<jats:italic>PNPLA3<\/jats:italic>) I148M\u2010rs738409, methylenetetrahydrofolate reductase (<jats:italic>MTHFR<\/jats:italic>) Ala222Val\u2010rs1801133, and aldehyde dehydrogenase 2 (<jats:italic>ALDH2<\/jats:italic>) Glu504Lys\u2010rs671 on the outcomes of Taiwanese patients with steatotic liver disease (SLD) have remained elusive. An 8\u2010year prospective cohort study of patients with (<jats:italic>n<\/jats:italic>\u2009=\u2009546) and without (<jats:italic>n<\/jats:italic>\u2009=\u2009580) SLD (controls) was undertaken in a Taiwanese tertiary care center. The 546 SLD patients comprised 306 (56.0%) men and 240 (44.0%) women with mean ages of 53.3 and 56.4\u2009years, respectively. Compared with the controls, SLD patients had an increased frequency of the <jats:italic>PNPLA3<\/jats:italic> I148M\u2010rs738409 GG genotype (25.5 vs. 5.9%, <jats:italic>p<\/jats:italic>\u2009=\u20090.001). Among the SLD patients, 236 (43.1%) suffered cardiovascular events, 52 (9.5%) showed extrahepatic cancers, 13 (2.38%) experienced hepatic events, including hepatocellular carcinoma (<jats:italic>n<\/jats:italic>\u2009=\u20093, 0.5%) and liver cirrhosis (<jats:italic>n<\/jats:italic>\u2009=\u20098, 1.47%), and none died. The Fibrosis\u20104 (FIB\u20104) scores were associated with extrahepatic cancer (hazard ratio [HR] 1.325; 95% confidence interval [CI], 1.038\u20131.691) and cirrhosis development (HR 1.532; 95% CI, 1.055\u20132.224), and the <jats:italic>PNPLA3<\/jats:italic> I148M\u2010rs738409 G allele (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.158, 95% CI, 0.054\u20130.325) was associated with the FIB\u20104 score. Stratified analyses showed that the impact of the FIB\u20104 score on extrahepatic cancer development was evident only in SLD patients with the <jats:italic>PNPLA3<\/jats:italic> I148M\u2010rs738409 GG genotype (HR 1.543; 95% CI, 1.195\u20131.993) and not in patients with the GC or CC genotype. Moreover, the <jats:italic>ALDH2<\/jats:italic> Glu504Lys\u2010rs671 G allele had a dose\u2010dependent effect on alcoholism, and the <jats:italic>MTHFR<\/jats:italic> and <jats:italic>ALDH2<\/jats:italic> genotypes were not significantly associated with SLD patient outcomes. In conclusion, special vigilance should be exercised for emerging extrahepatic cancer in SLD patients with the <jats:italic>PNPLA3<\/jats:italic> I148M\u2010rs738409 GG genotype and high FIB\u20104 scores.<\/jats:p>","DOI":"10.1111\/cas.16042","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T20:57:07Z","timestamp":1702414627000},"page":"564-574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Association of liver fibrosis with extrahepatic cancer in steatotic liver disease patients with PNPLA3 I148M GG genotype"],"prefix":"10.1111","volume":"115","author":[{"given":"Jennifer","family":"Tai","sequence":"first","affiliation":[{"name":"Department of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital  Linkou Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao\u2010Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital  Linkou Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital  Linkou Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sien\u2010Sing","family":"Yang","sequence":"additional","affiliation":[{"name":"Liver Center, Cathay General Hospital Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Hsun","family":"Chiu","sequence":"additional","affiliation":[{"name":"Molecular Infectious Disease Research Center Chang Gung Memorial Hospital at Linkou  Taoyuan Taiwan"},{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics Chang Gung Memorial Hospital at Linkou  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong\u2010Nan","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital  Linkou Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4902-4401","authenticated-orcid":false,"given":"Ming\u2010Ling","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital  Linkou Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,11]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.171"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1999.01377.x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000520"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-020-10094-2"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.04.043"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.08.011"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00003-1"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15738"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.12.002"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.03.011"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14543"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154337"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI122064"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nutd.2016.17"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-200609000-00016"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/v14091858"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02526.x"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soard.2014.07.016"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2019.03.016"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2011.01534.x"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2017.08.010"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agad015"},{"issue":"4","key":"e_1_2_13_24_1","first-page":"412","article-title":"Alcoholic hepatitis: diagnosis and management","volume":"105","author":"Keating M","year":"2022","journal-title":"Am Fam Physician"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v6.i9.626"},{"issue":"3","key":"e_1_2_13_26_1","first-page":"440","article-title":"Prevalence of methylene tetrahydrofolate reductase polymorphism in south Indian population","volume":"86","author":"Devi ARR","year":"2004","journal-title":"Curr Sci"},{"key":"e_1_2_13_27_1","first-page":"5649","article-title":"Simple and reliable genotyping of ALDH2 rs671 in the patients with acute alcoholism intoxication using tetra\u2010primer ARMS PCR","volume":"10","author":"Jiang S","year":"2017","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.01.018"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12731"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30154-2"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1805"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001072"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0009"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.01.006"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.10.007"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16763"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23622"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14595"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/09674845.2018.1505187"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.050302"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.08.012"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2010.10.014"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.08.011"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast-2021-000817"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00380"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.82920"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1358525"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.127902"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.07.030"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10010029"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00335.2013"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31609"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.760971"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31032"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31772-0"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.16042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T07:22:52Z","timestamp":1710228172000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.16042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,11]]},"references-count":54,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/cas.16042"],"URL":"https:\/\/doi.org\/10.1111\/cas.16042","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,11]]},"assertion":[{"value":"2023-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}