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Nat Genet. 2016 May;48(5):563-8. doi: 10.1038/ng.3545. Epub 2016 Apr 11.

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

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
2
Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
3
Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
4
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
5
Bioinformed, LLC, Gaithersburg, Maryland, USA.
6
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
7
Division of Genetics and Epidemiology, Institute for Cancer Research, London, UK.
8
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
9
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
10
Quantitative Genomic Medicine Laboratory, qGenomics, Barcelona, Spain.
11
Biostatistics and Epidemiology Section, Dartmouth Medical School, Lebanon, New Hampshire, USA.
12
Vermont Cancer Registry, Burlington, Vermont, USA.
13
Maine Cancer Registry, Augusta, Maine, USA.
14
Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
15
Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
16
Laboratory of Experimental Immunology, Center for Cancer Research, NCI-Frederick, Frederick, Maryland, USA.

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)).

PMID:
27064253
PMCID:
PMC4848121
DOI:
10.1038/ng.3545
[Indexed for MEDLINE]
Free PMC Article

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