Mosaic loss of chromosome Y is associated with common variation near TCL1A
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- dc.contributor.author Zhou, W.ca
- dc.contributor.author Real, Francisco X.ca
- dc.contributor.author Rodríguez Santiago, Benjamínca
- dc.contributor.author Pérez Jurado, Luis Albertoca
- dc.contributor.author Chanock, Stephen J.ca
- dc.date.accessioned 2016-07-20T11:43:42Z
- dc.date.issued 2016
- dc.description.abstract Mosaic loss of chromosome Y (mLOY) leading to gonosomal XY/XO commonly occurs during aging, particularly in smokers. We investigated whether mLOY was associated with non-hematological cancer in three prospective cohorts (8,679 cancer cases and 5,110 cancer-free controls) and genetic susceptibility to mLOY. Overall, mLOY was observed in 7% of men, and its prevalence increased with age (per-year odds ratio (OR) = 1.13, 95% confidence interval (CI) = 1.12-1.15; P < 2 × 10(-16)), reaching 18.7% among men over 80 years old. mLOY was associated with current smoking (OR = 2.35, 95% CI = 1.82-3.03; P = 5.55 × 10(-11)), but the association weakened with years after cessation. mLOY was not consistently associated with overall or specific cancer risk (for example, bladder, lung or prostate cancer) nor with cancer survival after diagnosis (multivariate-adjusted hazard ratio = 0.87, 95% CI = 0.73-1.04; P = 0.12). In a genome-wide association study, we observed the first example of a common susceptibility locus for genetic mosaicism, specifically mLOY, which maps to TCL1A at 14q32.13, marked by rs2887399 (OR = 1.55, 95% CI = 1.36-1.78; P = 1.37 × 10(-10)).ca
- dc.description.sponsorship This project has been funded in whole or in part with federal funds from the National Cancer Institute, US National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the US government.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Zhou W, Machiela MJ, Freedman ND, Rothman N, Malats N, Dagnall C. et al. Mosaic loss of chromosome Y is associated with common variation near TCL1A. Nat Genet. 2016 May;48(5):563-8. doi: 10.1038/ng.3545ca
- dc.identifier.doi http://dx.doi.org/10.1038/ng.3545
- dc.identifier.issn 1061-4036
- dc.identifier.uri http://hdl.handle.net/10230/27094
- dc.language.iso engca
- dc.publisher Nature Publishing Groupca
- dc.relation.ispartof Nature Genetics. 2016 May;48(5):563-8
- dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/ng.3545ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Cromosomes humans -- Anomaliesca
- dc.title Mosaic loss of chromosome Y is associated with common variation near TCL1Aca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca