{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:04:28Z","timestamp":1792191868580,"version":"4.4.0"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Physical activity reduces chronic disease risk and enhances immune function, but its causal relationship with thymic tumors\u2014rare neoplasms of the anterior mediastinum\u2014remains unclear. This study investigated whether physical activity reduces thymic tumor risk and whether circulating cytokines mediate this effect. We performed a two-sample Mendelian randomization (MR) analysis using genetic variants as instrumental variables for physical activity and cytokines. Data were obtained from large genome-wide association studies of Europeans, and included the following: physical activity (91,084 individuals), thymic tumors (473,681 individuals with 58 benign and 93 malignant cases), and cytokines (14,824 individuals). The inverse-variance weighted method served as the primary analysis. Genetically predicted physical activity was associated with reduced risks of benign (odds ratio [OR] = 0.381; 95% confidence interval [CI]: 0.158 to 0.921; p = 0.032) and malignant thymic tumors (OR = 0.312; 95% CI: 0.155 to 0.628; p = 0.001). Mediation analysis identified interleukin-10 receptor subunit \u03b2 (IL10RB) as a partial mediator, accounting for 5.95% of the protective effect on benign tumors. Sensitivity analyses indicated no pleiotropy or heterogeneity. In conclusion, physical activity causally reduces the risk of thymic tumors, partially mediated by IL10RB, highlighting its potential role in cancer prevention through immunomodulation.<\/jats:p>","DOI":"10.3390\/ijms252413485","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T12:09:28Z","timestamp":1734350968000},"page":"13485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Causal Relationship Between Physical Activity and Thymic Tumors Mediated by Circulating Cytokines: A Mendelian Randomization Mediation Analysis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2381-9961","authenticated-orcid":false,"given":"Yulin","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Sports Science, Hanyang University ERICA, Ansan 15588, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaipeng","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Sports Science, Hanyang University ERICA, Ansan 15588, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"i3857","DOI":"10.1136\/bmj.i3857","article-title":"Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: Systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013","volume":"354","author":"Kyu","year":"2016","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/cphy.c110025","article-title":"Lack of exercise is a major cause of chronic diseases","volume":"2","author":"Booth","year":"2012","journal-title":"Compr. 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