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

被引：126

作者：

Zhou, Weiyin ^{[1
,2
]}

Machiela, Mitchell J. ^{[1
]}

Freedman, Neal D. ^{[1
]}

Rothman, Nathaniel ^{[1
]}

Malats, Nuria ^{[3
]}

Dagnall, Casey ^{[1
,2
]}

Caporaso, Neil ^{[1
]}

Teras, Lauren T. ^{[4
]}

Gaudet, Mia M. ^{[4
]}

Gapstur, Susan M. ^{[4
]}

Stevens, Victoria L. ^{[4
]}

Jacobs, Kevin B. ^{[2
,5
]}

Sampson, Joshua ^{[1
]}

Albanes, Demetrius ^{[1
]}

Weinstein, Stephanie ^{[1
]}

Virtamo, Jarmo ^{[6
]}

Berndt, Sonja ^{[1
]}

Hoover, Robert N. ^{[1
]}

Black, Amanda ^{[1
]}

Silverman, Debra ^{[1
]}

Figueroa, Jonine ^{[1
]}

Garcia-Closas, Montserrat ^{[1
,7
]}

Real, Francisco X. ^{[3
,8
]}

Earl, Julie ^{[3
]}

Marenne, Gaelle ^{[3
]}

Rodriguez-Santiago, Benjamin ^{[8
,9
,10
]}

Karagas, Margaret ^{[11
]}

Johnson, Alison ^{[12
]}

Schwenn, Molly ^{[13
]}

Wu, Xifeng ^{[14
]}

Gu, Jian ^{[14
]}

Ye, Yuanqing ^{[14
]}

Hutchinson, Amy ^{[1
,2
]}

Tucker, Margaret ^{[1
]}

Perez-Jurado, Luis A. ^{[8
,9
,15
]}

Dean, Michael ^{[1
,16
]}

Yeager, Meredith ^{[1
,2
]}

Chanock, Stephen J. ^{[1
]}

机构：

[1] NCI, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA

[2] Leidos Biomed Res Inc, Canc Genom Res Lab, Frederick Natl Lab Canc Res, Frederick, MD USA

[3] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain

[4] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[5] Bioinformed LLC, Gaithersburg, MD USA

[6] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland

[7] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England

[8] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain

[9] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain

[10] QGenomics, Quantitat Genom Med Lab, Barcelona, Spain

[11] Dartmouth Med Sch, Biostat & Epidemiol Sect, Lebanon, NH USA

[12] Vermont Canc Registry, Burlington, VT USA

[13] Maine Canc Registry, Augusta, ME USA

[14] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[15] Hosp del Mar Res Inst IMIM, Barcelona, Spain

[16] NCI, Lab Expt Immunol, Ctr Canc Res, Frederick, MD 21701 USA

来源：

NATURE GENETICS | 2016年 / 48卷 / 05期

基金：

美国国家卫生研究院;

关键词：

DETECTABLE CLONAL MOSAICISM; BONE-MARROW-CELLS; CONFERS SUSCEPTIBILITY; JAK2; HAPLOTYPE; AGE; RISK; HEMATOPOIESIS; LEUKEMIA; BLOOD; SNP;

D O I：

10.1038/ng.3545

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 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 x 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 x 10(-10)).

引用

页码：563 / +

页数：8

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