Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

被引:91
作者
Wang, Zhaoming [1 ,18 ]
McGlynn, Katherine A. [1 ]
Rajpert-De Meyts, Ewa [2 ]
Bishop, D. Timothy [3 ]
Chung, Charles C. [1 ]
Dalgaard, Marlene D. [2 ,4 ]
Greene, Mark H. [1 ]
Gupta, Ramneek [4 ]
Grotmol, Tom [5 ]
Haugen, Trine B. [6 ]
Karlsson, Robert [7 ]
Litchfield, Kevin [8 ]
Mitra, Nandita [9 ]
Nielsen, Kasper [4 ]
Pyle, Louise C. [10 ,11 ]
Schwartz, Stephen M. [1 ,12 ]
Thorsson, Vesteinn [13 ]
Vardhanabhuti, Saran [14 ]
Wiklund, Fredrik [7 ]
Turnbull, Clare [8 ,15 ]
Chanock, Stephen J.
Kanetsky, Peter A. [16 ]
Nathanson, Katherine L. [10 ,17 ]
机构
[1] NCI, Div Canc Epidemiol & Genet, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[2] Copenhagen Univ Hosp, Rigshosp, Dept Growth & Reprod, Copenhagen, Denmark
[3] Univ Leeds, Leeds Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England
[4] Tech Univ Denmark, Dept Bio & Hlth Informat, Kongens Lyngby, Denmark
[5] Canc Registry Norway, Oslo, Norway
[6] Oslo & Akershus Univ, Fac Hlth Sci, Coll Appl Sci, Oslo, Norway
[7] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden
[8] Inst Canc Res, Div Genet & Epidemiol, London, England
[9] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA
[10] Univ Penn, Perelman Sch Med, Div Translat Med & Human Genet, Dept Med, Philadelphia, PA 19104 USA
[11] Childrens Hosp Philadelphia, Div Human Genet & Metab, Philadelphia, PA 19104 USA
[12] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA
[13] Inst Syst Biol, Seattle, WA USA
[14] Harvard Univ, Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA
[15] Genom England, London, England
[16] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA
[17] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA
[18] St Jude Childrens Res Hosp, Dept Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA
基金
美国国家卫生研究院;
关键词
CARCINOMA IN-SITU; SUSCEPTIBILITY LOCI; CANCER INCIDENCE; FAMILIAL RISK; EXPRESSION; HERITABILITY; RELATIVES; COMPONENT; VARIANTS; DISEASE;
D O I
10.1038/ng.3879
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 x 10(-8)). Most loci harbor biologically plausible candidate genes. We refined previously reported associations at 9p24.3 and 19p12 by identifying one and three additional independent SNPs, respectively. In aggregate, the 39 independent markers identified to date explain 37% of father-to-son familial risk, 8% of which can be attributed to the 12 new signals reported here. Our findings substantially increase the number of known TGCT susceptibility alleles, move the field closer to a comprehensive understanding of the underlying genetic architecture of TGCT, and provide further clues to the etiology of TGCT.
引用
收藏
页码:1141 / +
页数:8
相关论文
共 50 条
[1]   Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer [J].
Ahopelto, Kaisa ;
Bockelman, Camilla ;
Hagstrom, Jaana ;
Koskensalo, Selja ;
Haglund, Caj .
CANCER BIOLOGY & THERAPY, 2016, 17 (02) :163-168
[2]   Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling [J].
Almstrup, K ;
Hoei-Hansen, CE ;
Wirkner, U ;
Blake, J ;
Schwager, C ;
Ansorge, W ;
Nielsen, JE ;
Skakkebæk, NE ;
Meyts, ERD ;
Leffers, H .
CANCER RESEARCH, 2004, 64 (14) :4736-4743
[3]   A global reference for human genetic variation [J].
Altshuler, David M. ;
Durbin, Richard M. ;
Abecasis, Goncalo R. ;
Bentley, David R. ;
Chakravarti, Aravinda ;
Clark, Andrew G. ;
Donnelly, Peter ;
Eichler, Evan E. ;
Flicek, Paul ;
Gabriel, Stacey B. ;
Gibbs, Richard A. ;
Green, Eric D. ;
Hurles, Matthew E. ;
Knoppers, Bartha M. ;
Korbel, Jan O. ;
Lander, Eric S. ;
Lee, Charles ;
Lehrach, Hans ;
Mardis, Elaine R. ;
Marth, Gabor T. ;
McVean, Gil A. ;
Nickerson, Deborah A. ;
Wang, Jun ;
Wilson, Richard K. ;
Boerwinkle, Eric ;
Doddapaneni, Harsha ;
Han, Yi ;
Korchina, Viktoriya ;
Kovar, Christie ;
Lee, Sandra ;
Muzny, Donna ;
Reid, Jeffrey G. ;
Zhu, Yiming ;
Chang, Yuqi ;
Feng, Qiang ;
Fang, Xiaodong ;
Guo, Xiaosen ;
Jian, Min ;
Jiang, Hui ;
Jin, Xin ;
Lan, Tianming ;
Li, Guoqing ;
Li, Jingxiang ;
Li, Yingrui ;
Liu, Shengmao ;
Liu, Xiao ;
Lu, Yao ;
Ma, Xuedi ;
Tang, Meifang ;
Wang, Bo .
NATURE, 2015, 526 (7571) :68-+
[4]  
Bromen K, 2004, CANCER EPIDEM BIOMAR, V13, P1316
[5]   Risk of cancer in first- and second-degree relatives of testicular germ cell tumor cases and controls [J].
Chia, Victoria M. ;
Li, Yan ;
Goldin, Lynn R. ;
Graubard, Barry I. ;
Greene, Mark H. ;
Korde, Larissa ;
Rubertone, Mark V. ;
Erickson, Ralph L. ;
McGlynn, Katherine A. .
INTERNATIONAL JOURNAL OF CANCER, 2009, 124 (04) :952-957
[6]   Meta-analysis identifies four new loci associated with testicular germ cell tumor [J].
Chung, Charles C. ;
Kanetsky, Peter A. ;
Wang, Zhaoming ;
Hildebrandt, Michelle A. T. ;
Koster, Roelof ;
Skotheim, Rolf I. ;
Kratz, Christian P. ;
Turnbull, Clare ;
Cortessis, Victoria K. ;
Bakken, Anne C. ;
Bishop, D. Timothy ;
Cook, Michael B. ;
Erickson, R. Loren ;
Fossa, Sophie D. ;
Jacobs, Kevin B. ;
Korde, Larissa A. ;
Kraggerud, Sigrid M. ;
Lothe, Ragnhild A. ;
Loud, Jennifer T. ;
Rahman, Nazneen ;
Skinner, Eila C. ;
Thomas, Duncan C. ;
Wu, Xifeng ;
Yeager, Meredith ;
Schumacher, Fredrick R. ;
Greene, Mark H. ;
Schwartz, Stephen M. ;
McGlynn, Katherine A. ;
Chanock, Stephen J. ;
Nathanson, Katherine L. .
NATURE GENETICS, 2013, 45 (06) :680-+
[7]   Genome-wide linkage screen for testicular germ cell tumour susceptibility loci [J].
Crockford, GP ;
Linger, R ;
Hockley, S ;
Dudakia, D ;
Johnson, L ;
Huddart, R ;
Tucker, K ;
Friedlander, M ;
Phillips, KA ;
Hogg, D ;
Jewett, MAS ;
Lohynska, R ;
Daugaard, G ;
Richard, S ;
Chompret, A ;
Bonaïti-Pellié, C ;
Heidenreich, A ;
Albers, P ;
Olah, E ;
Geczi, L ;
Bodrogi, I ;
Ormiston, WJ ;
Daly, PA ;
Guilford, P ;
Fosså, SD ;
Heimdal, K ;
Tjulandin, SA ;
Liubchenko, L ;
Stoll, H ;
Weber, W ;
Forman, D ;
Oliver, T ;
Einhorn, L ;
McMaster, M ;
Kramer, J ;
Greene, MH ;
Weber, BL ;
Nathanson, KL ;
Cortessis, V ;
Easton, DF ;
Bishop, DT ;
Stratton, MR ;
Rapley, EA .
HUMAN MOLECULAR GENETICS, 2006, 15 (03) :443-451
[8]   A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation [J].
Dalgaard, Marlene D. ;
Weinhold, Nils ;
Edsgard, Daniel ;
Silver, Jeremy D. ;
Pers, Tune H. ;
Nielsen, John E. ;
Jorgensen, Niels ;
Juul, Anders ;
Gerds, Thomas A. ;
Giwercman, Aleksander ;
Giwercman, Yvonne L. ;
Cohn-Cedermark, Gabriella ;
Virtanen, Helena E. ;
Toppari, Jorma ;
Daugaard, Gedske ;
Jensen, Thomas S. ;
Brunak, Soren ;
Rajpert-De Meyts, Ewa ;
Skakkebk, Niels E. ;
Leffers, Henrik ;
Gupta, Ramneek .
JOURNAL OF MEDICAL GENETICS, 2012, 49 (01) :58-65
[9]   Improved whole-chromosome phasing for disease and population genetic studies [J].
Delaneau, Olivier ;
Zagury, Jean-Francois ;
Marchini, Jonathan .
NATURE METHODS, 2013, 10 (01) :5-6
[10]   Complex β-satellite repeat structures and the expansion of the zinc finger gene cluster in 19p12 [J].
Eichler, EE ;
Hoffman, SM ;
Adamson, AA .
GENOME RESEARCH, 1998, 8 (08) :791-808