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However, its relationship with treatment modalities remains unclear. In 348 prostate cancer patients at Juntendo University Hospital, local radiotherapy was associated with a higher prevalence of mLOY (OR\u2009=\u20092.55, 95% CI: 1.08\u20136.50, <jats:italic>P<\/jats:italic>\u2009=\u20090.04), whereas surgery and endocrine therapy were not. We then examined BioBank Japan data from over 30,000 patients with prostate, lung, colorectal, and gastric cancers. Fixed-effect meta-analysis across these sites showed a significant association between radiotherapy and mLOY (OR\u2009=\u20091.48, 95% CI: 1.11\u20131.98, <jats:italic>P<\/jats:italic>\u2009=\u20090.01). No significant effect heterogeneity was observed across cancer types (Q\u2009=\u20090.36, <jats:italic>I<\/jats:italic>\u00b2\u2009=\u20090%, <jats:italic>P<\/jats:italic>\u2009=\u20090.95). Our findings suggest that radiotherapy may exacerbate genomic instability, indicating a potential vulnerability in certain cancer patients to DNA damage induced by radiation therapy.<\/jats:p>","DOI":"10.1038\/s41514-025-00261-w","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:36:15Z","timestamp":1753806975000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging"],"prefix":"10.1038","volume":"11","author":[{"given":"Takuro","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Hachiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Ikehata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"China","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruna","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisamitsu","family":"Ide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Isotani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuko","family":"Nojiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Iwami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Uchiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Okazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidewaki","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Morisaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Kamatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikashi","family":"Terao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Horie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"261_CR1","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nrg3424","volume":"14","author":"LG Biesecker","year":"2013","unstructured":"Biesecker, L. 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