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

Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo, Japan. · pubmed

Paper

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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Research summary

Local radiotherapy is associated with an increased prevalence of mosaic loss of chromosome Y in prostate cancer patients. The study explores a potential link between cancer treatment and genomic instability, which could have implications for understanding aging processes and their relationship with cancer therapies.

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