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This study aims to elucidate the contribution of cellular senescence\u2010related genes to disease etiology. We investigated a cohort study of 439,501 individuals, which included 22 cancers and 9 non\u2010cancer diseases. We found that\n                    <jats:italic>HLA\u2010E<\/jats:italic>\n                    and\n                    <jats:italic>HLA\u2010G<\/jats:italic>\n                    \u2010associated senescence in epithelial and immune cells were specific oncogenic factors for prostate and lung cancers.\n                    <jats:italic>MAP2K4<\/jats:italic>\n                    was implicated as a risk factor for breast cancer, while\n                    <jats:italic>ZFP36L1<\/jats:italic>\n                    and\n                    <jats:italic>STAT3<\/jats:italic>\n                    were associated with a reduced risk of inflammatory bowel disease (IBD). Notably,\n                    <jats:italic>ETS2<\/jats:italic>\n                    \u2010mediated inhibition of the senescence\u2010associated secretory phenotype (SASP) was associated with decreased disease risk. Furthermore, single\u2010cell level analysis confirmed that the dynamics of these marked gene expressions in immune cells was related to reduced disease risk, while upregulation in epithelial cells correlated with increased disease risk. In parallel, co\u2010localization analyses corroborated these associations, explaining potential regulatory mechanisms underlying disease risk variants. These findings enhance our understanding of how cellular senescence works on disease susceptibility and provide potential targets for therapeutic interventions and precision medicine approaches.\n                  <\/jats:p>","DOI":"10.1002\/mc.70170","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T18:33:01Z","timestamp":1788114781000},"page":"1478-1494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omic Analysis of Putative Cellular Senescence\u2010Associated Genes on the Risk of Pan\u2010Cancer"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1336-8387","authenticated-orcid":false,"given":"Bin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China"},{"name":"Henan Key Laboratory for Helicobacter Pylori and Digestive 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