Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging

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

Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging

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

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

3 被引用数 (Scopus)

抄録

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.

本文言語	英語
論文番号	69
ジャーナル	npj Aging
巻	11
号	1
DOI	https://doi.org/10.1038/s41514-025-00261-w
出版ステータス	出版済み - 12-2025
外部発表	はい

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この成果は、次の持続可能な開発目標に貢献しています

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All Science Journal Classification (ASJC) codes

加齢科学
老年医学

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10.1038/s41514-025-00261-w

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Kobayashi, T., Hachiya, T., Lu, Y., Ikehata, Y., China, T., Kawano, H., Nagata, M., Ide, H., Isotani, S., Nojiri, S., Iwami, T., Uchiyama, S., Okazaki, Y., Nakagawa, H., Morisaki, T., Matsuda, K., Kamatani, Y., Terao, C., & Horie, S. (2025). Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging. npj Aging, 11(1), 記事 69. https://doi.org/10.1038/s41514-025-00261-w

@article{974a136492134dfd92b6f3b2f6ccc145,

title = "Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging",

abstract = "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{\textendash}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{\textendash}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.",

author = "Takuro Kobayashi and Tsuyoshi Hachiya and Yan Lu and Yoshihiro Ikehata and Toshiyuki China and Haruna Kawano and Masayoshi Nagata and Hisamitsu Ide and Shuji Isotani and Shuko Nojiri and Takuro Iwami and Shunsuke Uchiyama and Yasushi Okazaki and Hidewaki Nakagawa and Takayuki Morisaki and Koichi Matsuda and Yoichiro Kamatani and Chikashi Terao and Shigeo Horie",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41514-025-00261-w",

language = "English",

volume = "11",

journal = "npj Aging",

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Kobayashi, T, Hachiya, T, Lu, Y, Ikehata, Y, China, T, Kawano, H, Nagata, M, Ide, H, Isotani, S, Nojiri, S, Iwami, T, Uchiyama, S, Okazaki, Y, Nakagawa, H, Morisaki, T, Matsuda, K, Kamatani, Y, Terao, C & Horie, S 2025, 'Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging', npj Aging, vol. 11, no. 1, 69. https://doi.org/10.1038/s41514-025-00261-w

TY - JOUR

T1 - Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging

AU - Kobayashi, Takuro

AU - Hachiya, Tsuyoshi

AU - Lu, Yan

AU - Ikehata, Yoshihiro

AU - China, Toshiyuki

AU - Kawano, Haruna

AU - Nagata, Masayoshi

AU - Ide, Hisamitsu

AU - Isotani, Shuji

AU - Nojiri, Shuko

AU - Iwami, Takuro

AU - Uchiyama, Shunsuke

AU - Okazaki, Yasushi

AU - Nakagawa, Hidewaki

AU - Morisaki, Takayuki

AU - Matsuda, Koichi

AU - Kamatani, Yoichiro

AU - Terao, Chikashi

AU - Horie, Shigeo

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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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UR - https://www.scopus.com/pages/publications/105012097855#tab=citedBy

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DO - 10.1038/s41514-025-00261-w

M3 - Article

AN - SCOPUS:105012097855

SN - 2731-6068

VL - 11

JO - npj Aging

JF - npj Aging

IS - 1

M1 - 69

ER -

Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging

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