You are here

Nat Genet DOI:10.1038/ng.2966

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

Publication TypeJournal Article
Year of Publication2014
AuthorsForsberg, LA, Rasi, C, Malmqvist, N, Davies, H, Pasupulati, S, Pakalapati, G, Sandgren, J, de Ståhl, TDiaz, Zaghlool, A, Giedraitis, V, Lannfelt, L, Score, J, Cross, NCP, Absher, D, Janson, ETiensuu, Lindgren, CM, Morris, AP, Ingelsson, E, Lind, L, Dumanski, JP
JournalNat Genet
Volume46
Issue6
Pages624-8
Date Published2014 Jun
ISSN1546-1718
KeywordsAged, 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
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.

URLhttp://dx.doi.org/10.1038/ng.2966
DOI10.1038/ng.2966
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24777449?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID24777449
Grant List098017 / / Wellcome Trust / United Kingdom
090532 / / Wellcome Trust / United Kingdom
WT090532 / / Wellcome Trust / United Kingdom
WT098017 / / Wellcome Trust / United Kingdom
086596/Z/08/Z / / Wellcome Trust / United Kingdom
WT064890 / / Wellcome Trust / United Kingdom