Publications

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

Author(s): 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,  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

Journal: Nat Genet

Date: 2016 May

Major Program(s) or Research Group(s): PLCO

PubMed ID: 27064253

PMC ID: PMC4848121

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)).