{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:55:51Z","timestamp":1791575751975,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To what extent environmental factors are associated with liver diseases and liver cancer among individuals with varying levels of genetic predisposition remains unknown. In 353,703 UK Biobank participants, a validated polygenic risk score (PRS) for liver steatosis (\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    ,\n                    <jats:italic>TM6SF2<\/jats:italic>\n                    ,\n                    <jats:italic>MBOAT7<\/jats:italic>\n                    ,\n                    <jats:italic>GCKR<\/jats:italic>\n                    , and\n                    <jats:italic>HSD17B13<\/jats:italic>\n                    variants) and an environmental risk score (ERS) from six known risk factors (obesity, type 2 diabetes mellitus, smoking, frequent alcohol intake, physical inactivity, and infrequent coffee intake) were calculated. Incident outcomes were identified from hospital records and cancer registries. The genetics by environment (G\u2009\u00d7\u2009E) interactions and population attributable risks (PARs) for each ERS tertile were calculated, stratified by PRS tertile. We identified 3801 MASLD, 3458 liver cirrhosis, and 674 liver cancer in a median 13.6\u2010year follow\u2010up. PRS contributes 13.3% (95%CI: 10.8\u201315.9%) for MASLD, 8.2% (5.5\u201310.9%) for cirrhosis, and 14.7% (8.6\u201320.7%) for liver cancer. ERS contributes 34.1% (32.1\u201336.1%) for MASLD, 25.6% (23.1\u201328.1%) for cirrhosis, and 25.4% (19.2\u201331.5%) for liver cancer. Significant G\u2009\u00d7\u2009E interactions (\n                    <jats:italic>p<\/jats:italic>\n                    \u2010interaction &lt;.05) were found for liver cirrhosis and liver cancer where risk attributed to ERS was greater in the high versus the low PRS tertile. For liver cancer, PAR of the high versus low ERS was 36.5% (27.3\u201345.0%) in the high PRS tertile, compared to 16.5% (4.7\u201327.9%) in the low PRS tertile. High environmental risk showed greater contributions among participants with high genetic risk for liver cirrhosis and liver cancer. These stronger G\u2009\u00d7\u2009E interactions in clinically severe liver diseases underscore the importance of risk stratification and precision medicine.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70259","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T04:09:53Z","timestamp":1764907793000},"page":"2317-2328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The impact of genetic and environmental risk factors on adverse liver outcomes"],"prefix":"10.1002","volume":"158","author":[{"given":"Xinyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longgang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yale School of Nursing  Orange Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Yale School of Nursing  Orange Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Public Health and Emergency Management, School of Medicine Southern University of Science and Technology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Human Phenome Institute Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-2577","authenticated-orcid":false,"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Big Data in Health Science School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7365-2689","authenticated-orcid":false,"given":"Wanshui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nutrition School of Public Health, Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangao","family":"Fan","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6580-450X","authenticated-orcid":false,"given":"Jessica L.","family":"Petrick","sequence":"additional","affiliation":[{"name":"Slone Epidemiology Center Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-9933","authenticated-orcid":false,"given":"Katherine A.","family":"McGlynn","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-8508","authenticated-orcid":false,"given":"Xuehong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yale School of Nursing  Orange Connecticut USA"},{"name":"Yale School of Public Health  New Haven Connecticut USA"},{"name":"Department of Nutrition Harvard T.H. 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