{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:26:30Z","timestamp":1791354390085,"version":"4.3.1"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"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":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pleural mesothelioma (PM) is a lethal cancer primarily caused by asbestos exposure. Not all exposed individuals develop PM, suggesting the involvement of additional factors. This underscores the need for robust predictive models integrating biomarkers from multi\u2010omic domains to improve risk stratification and early detection. We developed and evaluated polygenic risk scores (PRS) and methylation risk scores (MRS) using a retrospective case\u2013control study (749 participants: 387 PM cases, 362 controls) and a nested case\u2013control European Prospective Investigation into Cancer and Nutrition (EPIC)\u2010Meso study (268 participants: 134 preclinical PM cases, 134 matched controls) within the EPIC cohort. Genome\u2010wide association analyses in the retrospective case\u2013control study identified PM\u2010associated variants. The PRS (1123 SNPs with\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) in the retrospective training subset stratified disease risk in the test set (ORs 3.46\u20139.54 across top percentiles) and improved model discrimination (AUC\u2009=\u20090.75 vs. 0.71 in baseline model,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04). In EPIC\u2010Meso, PRS performance was limited (AUC\u2009=\u20090.52). External validation in the UK\u2010Biobank (UKBB) confirmed a modest but consistent association with PM\u2010risk. A Meta\u2010PRS derived from the UKBB\u2010FinnGen meta\u2010analysis replicated this trend in the full retrospective dataset, showing higher OR across top percentiles (2.5\u201312.3) and improved discrimination (AUC 0.74 vs. 0.72,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.016). MRS, with 68 differentially methylated CpGs (effect\u2010size &gt;|0.10|, FDR\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) in the retrospective training set, increased the AUC from 0.66 to 0.85 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) in the test set and from 0.51 to 0.62 in EPIC\u2010Meso. PRS was most predictive in low\u2010exposure groups, while MRS remained robust across exposure levels. Combined PRS\u2010MRS models improved discrimination. Integrating multi\u2010omic biomarkers can enhance PM\u2010risk stratification and support earlier, targeted interventions in high\u2010risk asbestos\u2010exposed groups.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70316","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T06:29:15Z","timestamp":1767162555000},"page":"2866-2879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating polygenic and methylation risk scores for pleural mesothelioma risk stratification"],"prefix":"10.1002","volume":"158","author":[{"given":"Khadija Sana","family":"Hafeez","sequence":"first","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7573-3693","authenticated-orcid":false,"given":"Carla","family":"Debernardi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Allione","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6349-1764","authenticated-orcid":false,"given":"Elton Jalis","family":"Herman","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4400-1817","authenticated-orcid":false,"given":"Simonetta","family":"Guarrera","sequence":"additional","affiliation":[{"name":"Italian Institute for Genomic Medicine, IIGM  Turin Italy"},{"name":"Candiolo Cancer Institute FPO, FPO\u2010IRCCS  Candiolo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Unit of Medical Statistics and Cancer Epidemiology University of Eastern Piedmont, CPO\u2010Piedmont  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Aspesi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 del Piemonte Orientale  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Sculco","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 del Piemonte Orientale  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"La Vecchia","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 del Piemonte Orientale  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-5096","authenticated-orcid":false,"given":"Carlotta","family":"Sacerdote","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 del Piemonte Orientale  Novara Italy"},{"name":"Epidemiology Unit, Local Health Authority Novara  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Grosso","sequence":"additional","affiliation":[{"name":"Mesothelioma Unit, AO SS. Antonio e Biagio e Cesare Arrigo  Alessandria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Lill","sequence":"additional","affiliation":[{"name":"Ageing Epidemiology Research Unit, School of Public Health Imperial College  London UK"},{"name":"Institute of Epidemiology and Social Medicine, University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-9069","authenticated-orcid":false,"given":"Giovanna","family":"Masala","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Unit, Institute for Cancer Research Prevention and Clinical Network (Ispro)  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Guevara","sequence":"additional","affiliation":[{"name":"Navarra Institute of Public and Labor Health  Pamplona Spain"},{"name":"Center for Biomedical Research in Epidemiology and Public Health (Ciberesp)  Madrid Spain"},{"name":"Navarra Institute for Health Research (Idisna)  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias B.","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology German Institute of Human Nutrition Potsdam\u2010Rehbruecke  Nuthetal Germany"},{"name":"Institute of Nutritional Science, University of Potsdam  Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Panico","sequence":"additional","affiliation":[{"name":"Federico Ii University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaszan","family":"Asgari","sequence":"additional","affiliation":[{"name":"Paris\u2010Saclay University, Uvsq, Inserm, Gustave Roussy, Cesp  Villejuif 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