{"title":"癌症患者的局部放疗与Y染色体镶嵌丢失有关，这是男性衰老的标志。","authors":"Takuro Kobayashi, Tsuyoshi Hachiya, Yan Lu, Yoshihiro Ikehata, Toshiyuki China, Haruna Kawano, Masayoshi Nagata, Hisamitsu Ide, Shuji Isotani, Shuko Nojiri, Takuro Iwami, Shunsuke Uchiyama, Yasushi Okazaki, Hidewaki Nakagawa, Takayuki Morisaki, Koichi Matsuda, Yoichiro Kamatani, Chikashi Terao, Shigeo Horie","doi":"10.1038/s41514-025-00261-w","DOIUrl":null,"url":null,"abstract":"<p><p>Mosaic loss of chromosome Y (mLOY) is the most common somatic mutation in hematopoietic cells of aging men and is linked to cancer risk and mortality. 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 = 2.55, 95% CI: 1.08-6.50, P = 0.04), 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 = 1.48, 95% CI: 1.11-1.98, P = 0.01). No significant effect heterogeneity was observed across cancer types (Q = 0.36, I² = 0%, P = 0.95). Our findings suggest that radiotherapy may exacerbate genomic instability, indicating a potential vulnerability in certain cancer patients to DNA damage induced by radiation therapy.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"11 1","pages":"69"},"PeriodicalIF":6.0000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307641/pdf/","citationCount":"0","resultStr":"{\"title\":\"Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging.\",\"authors\":\"Takuro Kobayashi, Tsuyoshi Hachiya, Yan Lu, Yoshihiro Ikehata, Toshiyuki China, Haruna Kawano, Masayoshi Nagata, Hisamitsu Ide, Shuji Isotani, Shuko Nojiri, Takuro Iwami, Shunsuke Uchiyama, Yasushi Okazaki, Hidewaki Nakagawa, Takayuki Morisaki, Koichi Matsuda, Yoichiro Kamatani, Chikashi Terao, Shigeo Horie\",\"doi\":\"10.1038/s41514-025-00261-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Mosaic loss of chromosome Y (mLOY) is the most common somatic mutation in hematopoietic cells of aging men and is linked to cancer risk and mortality. 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 = 2.55, 95% CI: 1.08-6.50, P = 0.04), 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 = 1.48, 95% CI: 1.11-1.98, P = 0.01). No significant effect heterogeneity was observed across cancer types (Q = 0.36, I² = 0%, P = 0.95). Our findings suggest that radiotherapy may exacerbate genomic instability, indicating a potential vulnerability in certain cancer patients to DNA damage induced by radiation therapy.</p>\",\"PeriodicalId\":94160,\"journal\":{\"name\":\"npj aging\",\"volume\":\"11 1\",\"pages\":\"69\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307641/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj aging\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/s41514-025-00261-w\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj aging","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s41514-025-00261-w","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging.
Mosaic loss of chromosome Y (mLOY) is the most common somatic mutation in hematopoietic cells of aging men and is linked to cancer risk and mortality. 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 = 2.55, 95% CI: 1.08-6.50, P = 0.04), 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 = 1.48, 95% CI: 1.11-1.98, P = 0.01). No significant effect heterogeneity was observed across cancer types (Q = 0.36, I² = 0%, P = 0.95). Our findings suggest that radiotherapy may exacerbate genomic instability, indicating a potential vulnerability in certain cancer patients to DNA damage induced by radiation therapy.
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