Kobayashi Takuro, Hachiya Tsuyoshi, Lu Yan, Ikehata Yoshihiro, China Toshiyuki, Kawano Haruna, Nagata Masayoshi, Ide Hisamitsu, Isotani Shuji, Nojiri Shuko, Iwami Takuro, Uchiyama Shunsuke, Okazaki Yasushi, Nakagawa Hidewaki, Morisaki Takayuki, Matsuda Koichi, Kamatani Yoichiro, Terao Chikashi, Horie Shigeo
Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Data Science and Informatics for Genetic Disorders, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
NPJ Aging. 2025 Jul 29;11(1):69. doi: 10.1038/s41514-025-00261-w.
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.
Y染色体镶嵌性缺失（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相关。然而，其与治疗方式的关系仍不明确。在顺天堂大学医院的348例前列腺癌患者中，局部放疗与mLOY的较高患病率相关（OR = 2.55，95%CI：1.08 - 6.50，P = 0.04），而手术和内分泌治疗则不然。然后，我们研究了来自日本生物银行的30000多名前列腺癌、肺癌、结直肠癌和胃癌患者的数据。对这些部位进行的固定效应荟萃分析显示，放疗与mLOY之间存在显著关联（OR = 1.48，95%CI：1.11 - 1.98, P = 0.01）。在不同癌症类型中未观察到显著的效应异质性（Q = 0.36，I² = 0%，P = 0.95）。我们的研究结果表明，放疗可能会加剧基因组不稳定性，这表明某些癌症患者可能对放射治疗引起的DNA损伤具有潜在的易感性。
