Mosaic loss of chromosome Y is associated with common variation near TCL1A

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 t...

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Autores: Zhou, W., Real, Francisco X., Rodríguez Santiago, Benjamín, Pérez Jurado, Luis Alberto, Chanock, Stephen J.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/27094
Acceso en línea:http://hdl.handle.net/10230/27094
http://dx.doi.org/10.1038/ng.3545
Access Level:acceso abierto
Palabra clave:Cromosomes humans -- Anomalies
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spelling Mosaic loss of chromosome Y is associated with common variation near TCL1AZhou, W.Real, Francisco X.Rodríguez Santiago, BenjamínPérez Jurado, Luis AlbertoChanock, Stephen J.Cromosomes humans -- AnomaliesMosaic 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)).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.Nature Publishing Group20162016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/27094http://dx.doi.org/10.1038/ng.3545reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNature Genetics. 2016 May;48(5):563-8© Nature Publishing Group. http://dx.doi.org/10.1038/ng.3545info:eu-repo/semantics/openAccessoai:recercat.cat:10230/270942026-05-29T05:05:01Z
dc.title.none.fl_str_mv Mosaic loss of chromosome Y is associated with common variation near TCL1A
title Mosaic loss of chromosome Y is associated with common variation near TCL1A
spellingShingle Mosaic loss of chromosome Y is associated with common variation near TCL1A
Zhou, W.
Cromosomes humans -- Anomalies
title_short Mosaic loss of chromosome Y is associated with common variation near TCL1A
title_full Mosaic loss of chromosome Y is associated with common variation near TCL1A
title_fullStr Mosaic loss of chromosome Y is associated with common variation near TCL1A
title_full_unstemmed Mosaic loss of chromosome Y is associated with common variation near TCL1A
title_sort Mosaic loss of chromosome Y is associated with common variation near TCL1A
dc.creator.none.fl_str_mv Zhou, W.
Real, Francisco X.
Rodríguez Santiago, Benjamín
Pérez Jurado, Luis Alberto
Chanock, Stephen J.
author Zhou, W.
author_facet Zhou, W.
Real, Francisco X.
Rodríguez Santiago, Benjamín
Pérez Jurado, Luis Alberto
Chanock, Stephen J.
author_role author
author2 Real, Francisco X.
Rodríguez Santiago, Benjamín
Pérez Jurado, Luis Alberto
Chanock, Stephen J.
author2_role author
author
author
author
dc.subject.none.fl_str_mv Cromosomes humans -- Anomalies
topic Cromosomes humans -- Anomalies
description 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)).
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/27094
http://dx.doi.org/10.1038/ng.3545
url http://hdl.handle.net/10230/27094
http://dx.doi.org/10.1038/ng.3545
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature Genetics. 2016 May;48(5):563-8
dc.rights.none.fl_str_mv © Nature Publishing Group. http://dx.doi.org/10.1038/ng.3545
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © Nature Publishing Group. http://dx.doi.org/10.1038/ng.3545
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
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