Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Meta-analysis identifies four new loci associated with testicular germ cell tumor

Nature Genetics volume 45, pages 680–685 (2013)Cite this article

Subjects

Abstract

We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12–1.26; P = 1.11 × 10−8), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14–1.29; P = 5.59 × 10−9), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18–1.34; P = 5.15 × 10−12) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18–1.33; P = 4.32 × 10−13 and rs7221274: OR = 1.20, 95% CI = 1.12–1.28; P = 4.04 × 10−9), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Regional association plots, recombination plots and LD structure for the four new TGCT susceptibility regions at 4q22.2, 7p22.3, 16q22.3 and 17q22.

Similar content being viewed by others

References

  1. Rosen, A., Jayram, G., Drazer, M. & Eggener, S.E. Global trends in testicular cancer incidence and mortality. Eur. Urol. 60, 374–379 (2011).

    Article  PubMed  Google Scholar 

  2. Howlader, N. et al. SEER Cancer Statistics Review, 1975–2009 (Vintage 2009 Populations) based on November 2011 SEER data submission, posted to the SEER web site, 2012 〈http://seer.cancer.gov/csr/1975_2009_pops09/〉 (2012).

  3. Stang, A. et al. Gonadal and extragonadal germ cell tumours in the United States, 1973–2007. Int. J. Androl. 35, 616–625 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. McGlynn, K.A. & Trabert, B. Adolescent and adult risk factors for testicular cancer. Nat. Rev. Urol. 9, 339–349 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Daling, J.R. et al. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer 115, 1215–1223 (2009).

    Article  PubMed  Google Scholar 

  6. Trabert, B., Sigurdson, A.J., Sweeney, A.M., Strom, S.S. & McGlynn, K.A. Marijuana use and testicular germ cell tumors. Cancer 117, 848–853 (2011).

    Article  PubMed  Google Scholar 

  7. Lacson, J.C. et al. Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer 118, 5374–5383 (2012).

    Article  CAS  PubMed  Google Scholar 

  8. Bromen, K. et al. Testicular, other genital, and breast cancers in first-degree relatives of testicular cancer patients and controls. Cancer Epidemiol. Biomarkers Prev. 13, 1316–1324 (2004).

    PubMed  Google Scholar 

  9. Chia, V.M. et al. Risk of cancer in first- and second-degree relatives of testicular germ cell tumor cases and controls. Int. J. Cancer 124, 952–957 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Heimdal, K. et al. Risk of cancer in relatives of testicular cancer patients. Br. J. Cancer 73, 970–973 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sonneveld, D.J. et al. Familial testicular cancer in a single-centre population. Eur. J. Cancer 35, 1368–1373 (1999).

    Article  CAS  PubMed  Google Scholar 

  12. Czene, K., Lichtenstein, P. & Hemminki, K. Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int. J. Cancer 99, 260–266 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Neale, R.E., Carriere, P., Murphy, M.F. & Baade, P.D. Testicular cancer in twins: a meta-analysis. Br. J. Cancer 98, 171–173 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Swerdlow, A.J., De Stavola, B.L., Swanwick, M.A. & Maconochie, N.E. Risks of breast and testicular cancers in young adult twins in England and Wales: evidence on prenatal and genetic aetiology. Lancet 350, 1723–1728 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. Braun, M.M., Ahlbom, A., Floderus, B., Brinton, L.A. & Hoover, R.N. Effect of twinship on incidence of cancer of the testis, breast, and other sites (Sweden). Cancer Causes Control 6, 519–524 (1995).

    Article  CAS  PubMed  Google Scholar 

  16. Kanetsky, P.A. et al. Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat. Genet. 41, 811–815 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rapley, E.A. et al. A genome-wide association study of testicular germ cell tumor. Nat. Genet. 41, 807–810 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Turnbull, C. et al. Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat. Genet. 42, 604–607 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kanetsky, P.A. et al. A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. Hum. Mol. Genet. 20, 3109–3117 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ferlin, A. et al. Variants in KITLG predispose to testicular germ cell cancer independently from spermatogenic function. Endocr. Relat. Cancer 19, 101–108 (2012).

    Article  CAS  PubMed  Google Scholar 

  21. Dalgaard, M.D. et al. A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation. J. Med. Genet. 49, 58–65 (2012).

    Article  PubMed  Google Scholar 

  22. Rajpert-de Meyts, E. & Hoei-Hansen, C.E. From gonocytes to testicular cancer: the role of impaired gonadal development. Ann. NY Acad. Sci. 1120, 168–180 (2007).

    Article  PubMed  CAS  Google Scholar 

  23. Chung, C.C. & Chanock, S.J. Current status of genome-wide association studies in cancer. Hum. Genet. 130, 59–78 (2011).

    Article  PubMed  Google Scholar 

  24. Park, J.H. et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat. Genet. 42, 570–575 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Moniot, B. et al. Hematopoietic prostaglandin D synthase (H-Pgds) is expressed in the early embryonic gonad and participates to the initial nuclear translocation of the SOX9 protein. Dev. Dyn. 240, 2335–2343 (2011).

    Article  CAS  PubMed  Google Scholar 

  26. Park, J.M. et al. Hematopoietic prostaglandin D synthase suppresses intestinal adenomas in ApcMin/+ mice. Cancer Res. 67, 881–889 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Rowbotham, S.P. et al. Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1. Mol. Cell 42, 285–296 (2011).

    Article  CAS  PubMed  Google Scholar 

  28. Costelloe, T. et al. The yeast Fun30 and human SMARCAD1 chromatin remodellers promote DNA end resection. Nature 489, 581–584 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schoor, M., Schuster-Gossler, K., Roopenian, D. & Gossler, A. Skeletal dysplasias, growth retardation, reduced postnatal survival, and impaired fertility in mice lacking the SNF2/SWI2 family member ETL1. Mech. Dev. 85, 73–83 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Adzhubei, I.A. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248–249 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gidekel, S., Pizov, G., Bergman, Y. & Pikarsky, E. Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell 4, 361–370 (2003).

    Article  CAS  PubMed  Google Scholar 

  32. Tsai, C.C., Su, P.F., Huang, Y.F., Yew, T.L. & Hung, S.C. Oct4 and Nanog directly regulate Dnmt1 to maintain self-renewal and undifferentiated state in mesenchymal stem cells. Mol. Cell 47, 169–182 (2012).

    Article  CAS  PubMed  Google Scholar 

  33. Cheng, L. et al. OCT4: biological functions and clinical applications as a marker of germ cell neoplasia. J. Pathol. 211, 1–9 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Clark, A.T. The stem cell identity of testicular cancer. Stem Cell Rev. 3, 49–59 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Koster, R. et al. Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer. J. Clin. Invest. 120, 3594–3605 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Skotheim, R.I. et al. Differentiation of human embryonal carcinomas in vitro and in vivo reveals expression profiles relevant to normal development. Cancer Res. 65, 5588–5598 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Altshuler, D.M. et al. Integrating common and rare genetic variation in diverse human populations. Nature 467, 52–58 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Kim, S., Sun, H., Tomchick, D.R., Yu, H. & Luo, X. Structure of human Mad1 C-terminal domain reveals its involvement in kinetochore targeting. Proc. Natl. Acad. Sci. USA 109, 6549–6554 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Guo, Y. et al. Functional evaluation of missense variations in the human MAD1L1 and MAD2L1 genes and their impact on susceptibility to lung cancer. J. Med. Genet. 47, 616–622 (2010).

    Article  CAS  PubMed  Google Scholar 

  40. Iwanaga, Y., Kasai, T., Kibler, K. & Jeang, K.T. Characterization of regions in hsMAD1 needed for binding hsMAD2. A polymorphic change in an hsMAD1 leucine zipper affects MAD1-MAD2 interaction and spindle checkpoint function. J. Biol. Chem. 277, 31005–31013 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Fu, X. et al. RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53 stability in response to DNA damage. Proc. Natl. Acad. Sci. USA 107, 4579–4584 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Liu, S. et al. RING finger and WD repeat domain 3 (RFWD3) associates with replication protein A (RPA) and facilitates RPA-mediated DNA damage response. J. Biol. Chem. 286, 22314–22322 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhao, J. et al. Mixed lineage kinase domain–like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc. Natl. Acad. Sci. USA 109, 5322–5327 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sun, L. et al. Mixed lineage kinase domain–like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148, 213–227 (2012).

    Article  CAS  PubMed  Google Scholar 

  45. Zeller, T. et al. Genetics and beyond—the transcriptome of human monocytes and disease susceptibility. PLoS ONE 5, e10693 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Ihara, M. et al. Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa. Dev. Cell 8, 343–352 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Kissel, H. et al. The Sept4 septin locus is required for sperm terminal differentiation in mice. Dev. Cell 8, 353–364 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. Greenbaum, M.P. et al. TEX14 is essential for intercellular bridges and fertility in male mice. Proc. Natl. Acad. Sci. USA 103, 4982–4987 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kuznetsov, S. et al. RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females. J. Cell Biol. 176, 581–592 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wu, J.Y. et al. Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking Camk4. Nat. Genet. 25, 448–452 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Karlberg, S., Tiitinen, A. & Lipsanen-Nyman, M. Failure of sexual maturation in Mulibrey nanism. N. Engl. J. Med. 351, 2559–2560 (2004).

    Article  CAS  PubMed  Google Scholar 

  52. Meindl, A. et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat. Genet. 42, 410–414 (2010).

    Article  CAS  PubMed  Google Scholar 

  53. Loveday, C. et al. Germline RAD51C mutations confer susceptibility to ovarian cancer. Nat. Genet. 44, 475–476 (2012).

    Article  CAS  PubMed  Google Scholar 

  54. Mondal, G., Ohashi, A., Yang, L., Rowley, M. & Couch, F.J. Tex14, a Plk1-regulated protein, is required for kinetochore-microtubule attachment and regulation of the spindle assembly checkpoint. Mol. Cell 45, 680–695 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ishida, A., Sueyoshi, N., Shigeri, Y. & Kameshita, I. Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases. Br. J. Pharmacol. 154, 729–740 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Avela, K. et al. Gene encoding a new RING–B-box–Coiled-coil protein is mutated in mulibrey nanism. Nat. Genet. 25, 298–301 (2000).

    Article  CAS  PubMed  Google Scholar 

  57. Karlberg, S. et al. Testicular failure and male infertility in the monogenic Mulibrey nanism disorder. J. Clin. Endocrinol. Metab. 96, 3399–3407 (2011).

    Article  CAS  PubMed  Google Scholar 

  58. Atkin, N.B. & Baker, M.C. Specific chromosome change i(12p) in testicular tumors? Lancet 2, 1349 (1982).

    Article  CAS  PubMed  Google Scholar 

  59. Rodriguez, E. et al. Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors. Cancer Res. 52, 2285–2291 (1992).

    CAS  PubMed  Google Scholar 

  60. Skotheim, R.I. et al. Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. Cell Oncol. 28, 315–326 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Schumacher, F.R. et al. Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23. Hum. Mol. Genet. published online; doi:10.1093/hmg/ddt109 (5 March 2013).

  62. Fearnhead, P. SequenceLDhot: detecting recombination hotspots. Bioinformatics 22, 3061–3066 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Fearnhead, P. & Donnelly, P. Approximate likelihood methods for estimating local recombination rates. J. R. Stat. Soc. B 64, 657–680 (2002).

    Article  Google Scholar 

  64. Crawford, D.C. et al. Evidence for substantial fine-scale variation in recombination rates across the human genome. Nat. Genet. 36, 700–706 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Li, N. & Stephens, M. Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data. Genetics 165, 2213–2233 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Luna, A. & Nicodemus, K.K. snp.plotter: an R-based SNP/haplotype association and linkage disequilibrium plotting package. Bioinformatics 23, 774–776 (2007).

    Article  CAS  PubMed  Google Scholar 

  67. Cox, A. et al. A common coding variant in CASP8 is associated with breast cancer risk. Nat. Genet. 39, 352–358 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Hemminki, K. & Li, X. Familial risk in testicular cancer as a clue to a heritable and environmental aetiology. Br. J. Cancer 90, 1765–1770 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ward, L.D. & Kellis, M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40, D930–D934 (2012).

    Article  CAS  PubMed  Google Scholar 

  70. Boyle, A.P. et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 22, 1790–1797 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations indicate endorsement by the US Government. We thank C. Berg and P. Prorok, Division of Cancer Prevention, NCI, the screening center investigators and the staff of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, T. Riley and staff at Information Management Services, Inc., and B. O'Brien and staff at Westat, Inc., for their contributions to the PLCO Cancer Screening Trial. We thank S. Ciosek, M. McDermoth and K. D'Andrea for expert assistance in conducting TestPAC. We thank L. Kolonel and L. Le Marchand for providing access to the Multiethnic Cohort aggressive prostate cancer scan, as well as J.P. Lewinger, M. Pike, D.J. Van Den Berg and K. Siegmund for technical and scientific contributions to the parent study at USC.

A portion of this work was supported by the Intramural Research Program of the NCI and by support services contract HHSN261200655004C with Westat, Inc. The Penn GWAS (UPENN) and replication effort for the TestPAC study were supported by the Abramson Cancer Center at the University of Pennsylvania and US National Institutes of Health grant R01CA114478 to P.A.K. and K.L.N. The replication effort for the ATLAS study was supported by US National Institutes of Health grant R01CA085914 to S.M.S. The analysis of the USC GWAS controls was supported by the Multiethnic Cohort Study (NCI U01-CA98758). The analyses of the USC GWAS testicular cases and the Familial Study were supported by the California Cancer Research Program (99-00505V-10260 and 03-00174VRS-30021) and by an NCI grant (R01CA102042) to V.K.C. and a Whittier Foundation award to the Norris Comprehensive Cancer Center. The study at MD Anderson was supported by the Center for Translational and Public Health Genomics of the Duncan Family Institute for Cancer Prevention and Risk Assessment and by an MD Anderson Senior Research Trust Fellowship to X.W. The UK testicular cancer study was supported by the Institute of Cancer Research, Cancer Research UK and the Wellcome Trust and made use of control data generated by the Wellcome Trust Case Control Consortium 2 (WTCCC2). Support was provided by the Norwegian Cancer Society to R.A.L. and R.I.S., by Health Region South-Eastern Norway to R.A.L. and S.D.F., and by the Norwegian ExtraFoundation for Health and Rehabilitation to S.D.F.

Author information

Author notes

  1. Christian P Kratz

    Present address: Present address: Center for Pediatrics and Adolescent Medicine, Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.,

  2. Charles C Chung, Peter A Kanetsky, Zhaoming Wang, Michelle A T Hildebrandt, Roelof Koster, Rolf I Skotheim, Christian P Kratz, Clare Turnbull and Victoria K Cortessis: These authors contributed equally to this work.

  3. Stephen J Chanock and Katherine L Nathanson: These authors jointly directed this work.

Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, US Department of Health and Human Services, National Cancer Institute (NCI), US National Institutes of Health, Bethesda, Maryland, USA

    Charles C Chung, Zhaoming Wang, Christian P Kratz, Michael B Cook, Kevin B Jacobs, Larissa A Korde, Jennifer T Loud, Meredith Yeager, Mark H Greene, Katherine A McGlynn & Stephen J Chanock

  2. Division of Cancer Epidemiology and Genetics, Cancer Genome Research Laboratory, SAIC-Frederick, NCI-Frederick, Frederick, Maryland, USA

    Charles C Chung, Zhaoming Wang, Kevin B Jacobs & Meredith Yeager

  3. Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Peter A Kanetsky & Katherine L Nathanson

  4. Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Peter A Kanetsky

  5. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Michelle A T Hildebrandt & Xifeng Wu

  6. Department of Medicine, Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Roelof Koster & Katherine L Nathanson

  7. Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

    Rolf I Skotheim, Anne C Bakken, Sigrid M Kraggerud & Ragnhild A Lothe

  8. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway

    Rolf I Skotheim, Anne C Bakken, Sigrid M Kraggerud & Ragnhild A Lothe

  9. Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK

    Clare Turnbull & Nazneen Rahman

  10. Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA

    Victoria K Cortessis, Duncan C Thomas & Fredrick R Schumacher

  11. Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St. James's University Hospital, Leeds, UK

    D Timothy Bishop

  12. Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

    R Loren Erickson

  13. Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Oslo, Norway

    Sophie D Fosså

  14. Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington, USA

    Larissa A Korde

  15. Department of Urology, Stanford University, Stanford, California, USA

    Eila C Skinner

  16. Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA

    Stephen M Schwartz

  17. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA

    Stephen M Schwartz

Authors
  1. Charles C Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter A Kanetsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhaoming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelle A T Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roelof Koster
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rolf I Skotheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christian P Kratz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Clare Turnbull
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Victoria K Cortessis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Anne C Bakken
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D Timothy Bishop
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Michael B Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. R Loren Erickson
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Sophie D Fosså
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kevin B Jacobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Larissa A Korde
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Sigrid M Kraggerud
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ragnhild A Lothe
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Jennifer T Loud
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Nazneen Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Eila C Skinner
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Duncan C Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Xifeng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Meredith Yeager
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Fredrick R Schumacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Mark H Greene
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Stephen M Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Katherine A McGlynn
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Stephen J Chanock
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Katherine L Nathanson
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.J.C. and K.L.N. supervised the overall study. P.A.K., M.A.T.H., C.P.K., V.K.C., A.C.B., D.T.B., M.B.C., R.L.E., S.D.F., L.A.K., S.M.K., N.R., E.C.S., X.W., M.H.G., S.M.S., K.A.M. and K.L.N. contributed to recruitment, study and data management. C.C.C., P.A.K., Z.W., M.A.T.H., R.K., R.I.S., C.T., K.B.J., R.A.L., J.T.L., D.C.T., M.Y. and F.R.S. contributed to genotyping or association analysis of individual studies. C.C.C., Z.W. and R.K. carried out the meta-analysis and the additional reported ENCODE analyses. C.C.C. and K.L.N. prepared the manuscript, together with P.A.K., R.K. and S.J.C., and all authors reviewed and contributed to the manuscript.

Corresponding author

Correspondence to Katherine L Nathanson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Note, Supplementary Tables 1–7 (PDF 278 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chung, C., Kanetsky, P., Wang, Z. et al. Meta-analysis identifies four new loci associated with testicular germ cell tumor. Nat Genet 45, 680–685 (2013). https://doi.org/10.1038/ng.2634

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.2634

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing