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A genome-wide association study of testicular germ cell tumor

Abstract

We conducted a genome-wide association study for testicular germ cell tumor (TGCT), genotyping 307,666 SNPs in 730 cases and 1,435 controls from the UK and replicating associations in a further 571 cases and 1,806 controls. We found strong evidence for susceptibility loci on chromosome 5 (per allele OR = 1.37 (95% CI = 1.19–1.58), P = 3 × 10−13), chromosome 6 (OR = 1.50 (95% CI = 1.28–1.75), P = 10−13) and chromosome 12 (OR = 2.55 (95% CI = 2.05–3.19), P = 10−31). KITLG, encoding the ligand for the receptor tyrosine kinase KIT, which has previously been implicated in the pathogenesis of TGCT and the biology of germ cells, may explain the association on chromosome 12.

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Figure 1: Lower BAK1 expression associated with the G allele of rs210138 in lymphoblastoid cell lines.

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Acknowledgements

We would like to thank the individuals with TGCT and the clinicians involved in their care for participation in this study. We would like to thank D. Dudakia, J. Pugh, H. McDonald and J. Marke for subject recruitment and database entry for the TGCT collections. We acknowledge NHS funding to the NIHR 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. D.F.E. is a Principal Research Fellow of Cancer Research UK, and the study was supported by the Institute of Cancer Research, Cancer Research UK and the Wellcome Trust.

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Contributions

E.A.R., D.T.B., D.F.E. and M.R.S. designed the study and obtained financial support. E.A.R., R.A.H., The UK Testicular Cancer Collaboration and M.R.S. coordinated the studies providing samples for stage 1 and stage 2. P.D. directed genotyping of stage 1. N.R. and C.T. directed genotyping of stage 2. R.L., A.R., D.H., S.H. and S.S. conducted genotyping of stage 2. E.T.D. and P.D. produced and analyzed gene expression data. A.A.A.O., J.M., J.N., D.T.B., C.T. and D.F.E. designed, coordinated and conducted statistical analyses. M.R.S. drafted the manuscript with substantial contributions from C.T., E.A.R. and D.F.E. All authors contributed to the final paper.

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Correspondence to Michael R Stratton.

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

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Supplementary Note, Supplementary Tables 1–5 and Supplementary Figure 1 (PDF 94 kb)

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Rapley, E., Turnbull, C., Al Olama, A. et al. A genome-wide association study of testicular germ cell tumor. Nat Genet 41, 807–810 (2009). https://doi.org/10.1038/ng.394

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