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Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer

Nature Genetics volume 42, pages 604–607 (2010)Cite this article

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Abstract

We conducted a genome-wide association study for testicular germ cell tumor, genotyping 298,782 SNPs in 979 affected individuals and 4,947 controls from the UK and replicating associations in a further 664 cases and 3,456 controls. We identified three new susceptibility loci, two of which include genes that are involved in telomere regulation. We identified two independent signals within the TERT-CLPTM1L locus on chromosome 5, which has previously been associated with multiple other cancers (rs4635969, OR = 1.54, P = 1.14 × 10−23; rs2736100, OR = 1.33, P = 7.55 × 10−15). We also identified a locus on chromosome 12 (rs2900333, OR = 1.27, P = 6.16 × 10−10) that contains ATF7IP, a regulator of TERT expression. Finally, we identified a locus on chromosome 9 (rs755383, OR = 1.37, P = 1.12 × 10−23), containing the sex determination gene DMRT1, which has been linked to teratoma susceptibility in mice.

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Figure 1: Regional plots of the three new TGCT loci.

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Acknowledgements

We thank subjects with TGCT and the clinicians involved in their care for participation in this study. We also thank D. Dudakia, J. Pugh, H. McDonald and J. Marke for recruitment of subjects and database entry for the TGCT collections. We acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Centre. We acknowledge use of DNA from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. C.T. is a Medical Research Council Clinical Research Fellow. D.F.E. is a Principal Research Fellow of Cancer Research UK. The study was supported by the Institute of Cancer Research, Cancer Research UK and the Wellcome Trust.

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Authors and Affiliations

  1. Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK

    Clare Turnbull, Elizabeth A Rapley, Sheila Seal, David Pernet, Anthony Renwick, Deborah Hughes, Michelle Ricketts, Rachel Linger, Michael R Stratton & Nazneen Rahman

  2. Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Leeds, UK

    Jeremie Nsengimana & D Timothy Bishop

  3. The Wellcome Trust Sanger Institute, Hinxton, UK

    Panagiotis Deloukas & Michael R Stratton

  4. Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey, UK

    Robert A Huddart

  5. Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK

    Douglas F Easton

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  1. Clare Turnbull
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Consortia

The UK Testicular Cancer Collaboration

Contributions

M.R.S., E.A.R., D.T.B. and D.F.E. designed the study and obtained financial support. N.R., E.A.R., R.A.H., U.K.T.C.C. and M.R.S. coordinated the studies and provided samples for stage 1 and stage 2. P.D. directed genotyping of stage 1. N.R. and C.T. directed genotyping of stage 2. S.S., E.A.R., R.L. and D.H. coordinated sample management and transfer. A.R., D.H., M.R., R.L. and S.S. conducted genotyping of stage 2. D.P. coordinated data transfer and storage. C.T. designed and conducted statistical analyses with D.F.E. C.T. and N.R. drafted the manuscript. All authors contributed to the final paper.

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Correspondence to Clare Turnbull.

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A full list of members is provided in the Supplementary Note.

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Supplementary Note, Supplementary Tables 1–9 and Supplementary Figure 1 (PDF 115 kb)

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Turnbull, C., Rapley, E., Seal, S. et al. Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat Genet 42, 604–607 (2010). https://doi.org/10.1038/ng.607

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