Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer
2014 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 6, 624-628 p.Article in journal, Letter (Refereed) Published
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.
Place, publisher, year, edition, pages
2014. Vol. 46, no 6, 624-628 p.
IdentifiersURN: urn:nbn:se:uu:diva-228467DOI: 10.1038/ng.2966ISI: 000336870700021OAI: oai:DiVA.org:uu-228467DiVA: diva2:734248