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

IF 6 Q2 GERIATRICS & GERONTOLOGY

npj aging Pub Date : 2025-07-29 DOI:10.1038/s41514-025-00261-w

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

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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: 1.08-6.50, 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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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。

Y染色体镶嵌缺失（mLOY）是老年男性造血细胞中最常见的体细胞突变，与癌症风险和死亡率有关。然而，其与治疗方式的关系尚不清楚。在Juntendo大学医院的348例前列腺癌患者中，局部放疗与较高的mLOY患病率相关（OR = 2.55, 95% CI: 1.08-6.50, P = 0.04），而手术和内分泌治疗与mLOY患病率无关。然后，我们检查了日本生物银行三万多名前列腺癌、肺癌、结直肠癌和胃癌患者的数据。这些部位的固定效应荟萃分析显示放疗与mLOY之间存在显著相关性（OR = 1.48, 95% CI: 1.11-1.98, P = 0.01）。不同癌症类型间未观察到显著的异质性（Q = 0.36, I²= 0%,P = 0.95）。我们的研究结果表明，放射治疗可能加剧基因组的不稳定性，表明某些癌症患者对放射治疗引起的DNA损伤具有潜在的脆弱性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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npj aging

CiteScore

8.90

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0.00%

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