Format

Send to

Choose Destination
Nat Genet. 2014 Jun;46(6):624-8. doi: 10.1038/ng.2966. Epub 2014 Apr 28.

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

Author information

1
1] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
2
1] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. [2] Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [3] Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
3
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
4
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
5
Faculty of Medicine, University of Southampton, Southampton, UK.
6
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
7
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
8
1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Broad Institute of MIT and Harvard University, Cambridge, Massachusetts, USA.
9
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
10
1] Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [2] Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Abstract

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.

PMID:
24777449
PMCID:
PMC5536222
DOI:
10.1038/ng.2966
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center