Research article2014Peer reviewedOpen access
Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer
Forsberg, Lars A.; Rasi, Chiara; Malmqvist, Niklas; Davies, Hanna; Pasupulati, Saichand; Pakalapati, Geeta; Sandgren, Johanna; de Stahl, Teresita Diaz; Zaghlool, Ammar; Giedraitis, Vilmantas; Lannfelt, Lars; Score, Joannah; Cross, Nicholas C. P.; Absher, Devin; Janson, Eva Tiensuu; Lindgren, Cecilia M.; Morris, Andrew P.; Ingelsson, Erik; Lind, Lars; Dumanski, Jan P.
Abstract
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.
Published in
Nature Genetics
2014, Volume: 46, number: 6, pages: 624-628
Publisher: NATURE PUBLISHING GROUP
UKÄ Subject classification
Cancer and Oncology
Publication identifier
DOI: https://doi.org/10.1038/ng.2966
Permanent link to this page (URI)
https://res.slu.se/id/publ/90736