Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer

Authors:
Top Cited Papers
Open Access
Publisher website
Google Scholar
Abstract
Lars Forsberg, Jan Dumanski and colleagues report that age-related loss of chromosome Y in peripheral blood is associated with increased risks of all-cause mortality, cancer mortality and non-hematological cancer mortality. Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained1,2. Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells3,4, but the phenotypic consequences of LOY have been elusive5,6,7,8,9,10. 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.

This publication has 40 references indexed in Scilit: