Abstract
Wilms tumor is the most common renal malignancy of childhood. To identify common variants that confer susceptibility to Wilms tumor, we conducted a genome-wide association study in 757 individuals with Wilms tumor (cases) and 1,879 controls. We evaluated ten SNPs in regions significantly associated at P < 5 × 10−5 in two independent replication series from the UK (769 cases and 2,814 controls) and the United States (719 cases and 1,037 controls). We identified clear significant associations at 2p24 (rs3755132, P = 1.03 × 10−14; rs807624, P = 1.32 × 10−14) and 11q14 (rs790356, P = 4.25 × 10−15). Both regions contain genes that are plausibly related to Wilms tumorigenesis. We also identified candidate association signals at 5q14, 22q12 and Xp22.
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Change history
06 June 2012
In the version of this article initially published, the name of one of the authors was incorrectly listed as James Nicholdson. The correct name is James Nicholson. The error has been corrected in the HTML and PDF versions of the article.
10 July 2013
In the version of this article initially published, the following statement was omitted from the Acknowledgments: "We acknowledge use of data from the database of Genotypes and Phenotypes (dbGaP) from the NCBI, US National Library of Medicine. Research support to collect data and develop an application to support High Density SNP Association Analysis of Melanoma (phs000187) was provided by grants 3P50CA093459, 5P50CA097007, 5R01ES011740 and 5R01CA133996 from the US National Institutes of Health. This study also used, in part, data from the National Institute of Neurological Disorders and Stroke (NINDS) dbGaP database from the CIDR:NGRC Parkinson's Disease Study (phs000196)." The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank the families and the physicians and nurses that recruited them for their participation in this study, which was funded by the Wellcome Trust Case Control Consortium 3 (WTCCC3) initiative (grant reference 088804/Z/09/Z). We thank P. Donnelly for statistical advice throughout the design and execution of the study. We thank D. Dudakia, J. Bull, R. Linger, B. Ebbs, D. Hughes from Institute of Cancer Research (ICR) and Y. Mistry (from the Children's Cancer and Leukaemia Group (CCLG) tumor bank) for assistance in sample collection, DNA extraction and genotyping. The US samples and data were provided by the Children's Oncology Group (study AREN09B1) supported by the Chair's grant U10 CA98543, SDC grant U10 CA98413 and Human Specimen Banking grant U24 CA114766 from the National Cancer Institute at the US National Institutes of Health. The UK samples were collected through the Factors Associated with Childhood Tumors (FACT) study, which is a CCLG Study (Multicentre Research Ethics Committee (MREC) 05/MRE02/17) and is supported by Cancer Research UK (grant references C8620/A9024 and C8620_A8857). A full list of collaborators is given in the Supplementary Note. The CCRG receives funding from the UK Department of Health, the National Cancer Intelligence Network, the Scottish Government and Children with Cancer UK. The views expressed in this publication are those of the authors and not necessarily of any of these organizations. We acknowledge use of DNA from the British 1958 Birth Cohort DNA collection. We acknowledge use of data from the database of Genotypes and Phenotypes (dbGaP) from the NCBI, US National Library of Medicine. Research support to collect data and develop an application to support High Density SNP Association Analysis of Melanoma (phs000187) was provided by grants 3P50CA093459, 5P50CA097007, 5R01ES011740 and 5R01CA133996 from the US National Institutes of Health. This study also used, in part, data from the National Institute of Neurological Disorders and Stroke (NINDS) dbGaP database from the CIDR:NGRC Parkinson's Disease Study (phs000196). We acknowledge NHS funding to the ICR/Royal Marsden Hospital (RMH)/National Institute for Health Research (NIHR) Specialist Biomedical Cancer Research Centre. I.S. is supported by Michael and Betty Kadoorie Cancer Genetics. C.T. is a Medical Research Council Clinical Research Fellow. This study was conducted at the Institution of Cancer Research, UK.
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N.R. and C.T. designed the study and obtained financial support. M.G., J.H., M.H., J.K., S.L., G.L., M.M., B.M., V.N., J.N., S.P., B.P., M.R., M.S., H.T. and N.R. undertook sample and data collection of UK cases, which was coordinated by A.Z., M.W.-P., K.P.-J., C.A.S. and N.R. A.N., J.D. and P.G. coordinated the transfer of US samples. E.R.P., S.S., R.M.M.-X., S.H., I.S. and A.R. coordinated sample management and replication genotyping and sequencing. D.P. coordinated data transfer and management. C.T. conducted statistical analyses with assistance from D.P. and E.R. C.T., E.R.P. and N.R. wrote the manuscript. N.R. and C.T. oversaw and managed all aspects of the study.
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Supplementary Table 1–7, Supplementary Figures 1 and 2 and Supplementary Note (PDF 205 kb)
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Turnbull, C., Perdeaux, E., Pernet, D. et al. A genome-wide association study identifies susceptibility loci for Wilms tumor. Nat Genet 44, 681–684 (2012). https://doi.org/10.1038/ng.2251
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DOI: https://doi.org/10.1038/ng.2251
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