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

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Forsberg, Lars A; Rasi, Chiara; Malmqvist, Niklas; Davies, Hanna; Pasupulati, Saichand; Pakalapati, Geeta; Sandgren, Johanna; Diaz de Ståhl, Teresita; 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
Year of Publication: 2014
Journal: Nat Genet
Volume: 46
Issue: 6
Pagination: 624-8
Date Published: 2014 Jun
Publication Language: eng
ISSN: 1546-1718
Keywords: Aged, Aged, 80 and over, Biomarkers, Tumor, Chromosome Aberrations, Chromosomes, Human, Y, Cohort Studies, Gene Deletion, Genetic Variation, Genotype, Humans, Male, Middle Aged, Mosaicism, Neoplasms, Phenotype, Proportional Hazards Models, Risk, Sex Factors

Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained. Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells, but the phenotypic consequences of LOY have been elusive. 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.

DOI: 10.1038/ng.2966
Alternate Journal: Nat. Genet.