Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer

被引:253
作者
Kanetsky, Peter A. [1 ,4 ]
Mitra, Nandita [1 ,4 ]
Vardhanabhuti, Saran [4 ]
Li, Mingyao [4 ]
Vaughn, David J. [1 ,2 ]
Letrero, Richard [1 ,3 ]
Ciosek, Stephanie L. [1 ,3 ]
Doody, David R. [5 ]
Smith, Lauren M. [3 ]
Weaver, JoEllen [6 ]
Albano, Anthony [7 ,8 ]
Chen, Chu [9 ]
Starr, Jacqueline R. [5 ,9 ,10 ]
Rader, Daniel J. [11 ,12 ]
Godwin, Andrew K. [6 ]
Reilly, Muredach P. [11 ,12 ]
Hakonarson, Hakon [7 ,8 ]
Schwartz, Stephen M. [5 ,9 ]
Nathanson, Katherine L. [1 ,3 ]
机构
[1] Univ Penn, Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Div Hematol Oncol, Dept Med, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Div Med Genet, Dept Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Dept Med, Philadelphia, PA 19104 USA
[5] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA
[6] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA
[7] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA
[8] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA
[9] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA
[10] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA
[11] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA
[12] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA
关键词
GENOME-WIDE ASSOCIATION; TUMOR SUSCEPTIBILITY; FACTOR-RECEPTOR; PROLIFERATION; PIGMENTATION; ACTIVATION; FERTILITY; MIGRATION; ETIOLOGY; HUMANS;
D O I
10.1038/ng.393
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Testicular germ cell tumors (TGCT) have been expected to have a strong underlying genetic component. We conducted a genome-wide scan among 277 TGCT cases and 919 controls and found that seven markers at 12p22 within KITLG (c-KIT ligand) reached genome-wide significance (P < 5.0 x 10 (-8) in discovery). In independent replication, TGCT risk was increased threefold per copy of the major allele at rs3782179 and rs4474514 (OR = 3.08, 95% CI = 2.29-4.13; OR = 3.07, 95% CI 2.29-4.13, respectively). We found associations with rs4324715 and rs6897876 at 5q31.3 near SPRY4 (sprouty 4; P < 5.0 x 10(-6) in discovery). In independent replication, risk of TGCT was increased nearly 40% per copy of the major allele (OR = 1.37, 95% CI = 1.14-1.64; OR = 1.39, 95% CI = 1.16-1.66, respectively). All of the genotypes were associated with both seminoma and nonseminoma TGCT subtypes. These results demonstrate that common genetic variants affect TGCT risk and implicate KITLG and SPRY4 as genes involved in TGCT susceptibility.
引用
收藏
页码:811 / U65
页数:6
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