TY - JOUR
T1 - Mosaic loss of chromosome Y is associated with common variation near TCL1A
AU - Zhou, Weiyin
AU - Machiela, Mitchell J.
AU - Freedman, Neal D.
AU - Rothman, Nathaniel
AU - Malats, Nuria
AU - Dagnall, Casey
AU - Caporaso, Neil
AU - Teras, Lauren T.
AU - Gaudet, Mia M.
AU - Gapstur, Susan M.
AU - Stevens, Victoria L.
AU - Jacobs, Kevin B.
AU - Sampson, Joshua
AU - Albanes, Demetrius
AU - Weinstein, Stephanie
AU - Virtamo, Jarmo
AU - Berndt, Sonja
AU - Hoover, Robert N.
AU - Black, Amanda
AU - Silverman, Debra
AU - Figueroa, Jonine
AU - Garcia-Closas, Montserrat
AU - Real, Francisco X.
AU - Earl, Julie
AU - Marenne, Gaelle
AU - Rodriguez-Santiago, Benjamin
AU - Karagas, Margaret
AU - Johnson, Alison
AU - Schwenn, Molly
AU - Wu, Xifeng
AU - Gu, Jian
AU - Ye, Yuanqing
AU - Hutchinson, Amy
AU - Tucker, Margaret
AU - Perez-Jurado, Luis A.
AU - Dean, Michael
AU - Yeager, Meredith
AU - Chanock, Stephen J.
N1 - Publisher Copyright:
© 2016 Nature America, Inc.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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 -6), 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 -1), 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 -0).
AB - 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 -6), 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 -1), 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 -0).
UR - http://www.scopus.com/inward/record.url?scp=84963522549&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963522549&partnerID=8YFLogxK
U2 - 10.1038/ng.3545
DO - 10.1038/ng.3545
M3 - Article
C2 - 27064253
AN - SCOPUS:84963522549
SN - 1061-4036
VL - 48
SP - 563
EP - 568
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -