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Mosaic loss of chromosome Y is associated with common variation near TCL1A.
Pubmed ID
27064253 (View this publication on the PubMed website)
Nat. Genet. 2016; Volume 48 (Issue 5): Pages 563-8
Zhou W, Machiela MJ, Freedman ND, Rothman N, Malats N, Dagnall C, Caporaso N, Teras LT, Gaudet MM, Gapstur SM, Stevens VL, Jacobs KB, Sampson J, Albanes D, Weinstein S, Virtamo J, Berndt S, Hoover RN, Black A, Silverman D, more Figueroa J, Garcia-Closas M, Real FX, Earl J, Marenne G, Rodriguez-Santiago B, Karagas M, Johnson A, Schwenn M, Wu X, Gu J, Ye Y, Hutchinson A, Tucker M, Perez-Jurado LA, Dean M, Yeager M, Chanock SJ
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
  • Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
  • Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
  • Biostatistics and Epidemiology Section, Dartmouth Medical School, Lebanon, New Hampshire, USA.
  • Vermont Cancer Registry, Burlington, Vermont, USA.
  • Maine Cancer Registry, Augusta, Maine, USA.
  • Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

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)).

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