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Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.ORCID iD: 0000-0002-1701-755X
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
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2014 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 6, 624-628 p.Article in journal, Letter (Refereed) Published
Abstract [en]

Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained(1,2). Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells(3,4), but the phenotypic consequences of LOY have been elusive(5-10). From analysis of 1,153 elderly men, we report that LOY in peripheral blood was associated with risks of all-cause mortality (hazards ratio (HR) = 1.91, 95% confidence interval (CI) = 1.17-3.13; 637 events) and non-hematological cancer mortality (HR = 3.62, 95% CI = 1.56-8.41; 132 events). LOY affected at least 8.2% of the subjects in this cohort, and median survival times among men with LOY were 5.5 years shorter. Association of LOY with risk of all-cause mortality was validated in an independent cohort (HR = 3.66) in which 20.5% of subjects showed LOY. These results illustrate the impact of post-zygotic mosaicism on disease risk, could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination. LOY in blood could become a predictive biomarker of male carcinogenesis.

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2014. Vol. 46, no 6, 624-628 p.
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Medical Genetics
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URN: urn:nbn:se:uu:diva-228467DOI: 10.1038/ng.2966ISI: 000336870700021OAI: oai:DiVA.org:uu-228467DiVA: diva2:734248
Available from: 2014-07-15 Created: 2014-07-15 Last updated: 2017-12-05Bibliographically approved

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Forsberg, Lars A.Rasi, ChiaraDavies, HannaZaghlool, AmmarGiedraitis, VilmantasLannfelt, LarsTiensuu Janson, EvaIngelsson, ErikLind, LarsDumanski, Jan P.

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Forsberg, Lars A.Rasi, ChiaraDavies, HannaZaghlool, AmmarGiedraitis, VilmantasLannfelt, LarsTiensuu Janson, EvaIngelsson, ErikLind, LarsDumanski, Jan P.
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Science for Life Laboratory, SciLifeLabMedicinsk genetik och genomikDepartment of Medical SciencesDepartment of Immunology, Genetics and PathologyGenomicsGeriatricsEndocrine OncologyMolecular epidemiologyCardiovascular epidemiology
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