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A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)

Nature Genetics volume 42, pages 1126–1130 (2010)Cite this article

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Abstract

To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.

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Figure 1: Genome-wide association results from the discovery phase.
Figure 2: Regional plots of association results and recombination rates for the 2p16.1, 8q24.21 and 10p14 susceptibility loci.

References

  1. Kuppers, R. The biology of Hodgkin's lymphoma. Nat. Rev. Cancer 9, 15–27 (2009).

    Article  Google Scholar 

  2. Swerdlow, A.J. Epidemiology of Hodgkin's disease and non-Hodgkin's lymphoma. Eur. J. Nucl. Med. Mol. Imaging 30 Suppl 1, S3–S12 (2003).

    Article  Google Scholar 

  3. Smith, A. et al. The Haematological Malignancy Research Network (HMRN): a new information strategy for population based epidemiology and health service research. Br. J. Haematol. 148, 739–753 (2010).

    Article  Google Scholar 

  4. Kutok, J.L. & Wang, F. Spectrum of Epstein-Barr virus–associated diseases. Annu. Rev. Pathol. 1, 375–404 (2006).

    Article  CAS  Google Scholar 

  5. Goldin, L.R. et al. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer 100, 1902–1908 (2004).

    Article  Google Scholar 

  6. Amiel, J. Study of the leukocyte phenotypes in Hodgkin's disease. in Histocompatibility Testing (ed, Teraski, P.I.) (Munksgaard, Copenhagen, Denmark, 1967).

  7. Klitz, W., Aldrich, C.L., Fildes, N., Horning, S.J. & Begovich, A.B. Localization of predisposition to Hodgkin disease in the HLA class II region. Am. J. Hum. Genet. 54, 497–505 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Oza, A.M. et al. A clinical and epidemiological study of human leukocyte antigen-DPB alleles in Hodgkin's disease. Cancer Res. 54, 5101–5105 (1994).

    CAS  PubMed  Google Scholar 

  9. Hjalgrim, H. et al. HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma. Proc. Natl. Acad. Sci. USA 107, 6400–6405 (2010).

    Article  CAS  Google Scholar 

  10. Niens, M. et al. HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma. Blood 110, 3310–3315 (2007).

    Article  CAS  Google Scholar 

  11. Risch, N. Assessing the role of HLA-linked and unlinked determinants of disease. Am. J. Hum. Genet. 40, 1–14 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Goldin, L.R. et al. A genome screen of families at high risk for Hodgkin lymphoma: evidence for a susceptibility gene on chromosome 4. J. Med. Genet. 42, 595–601 (2005).

    Article  CAS  Google Scholar 

  13. Mack, T.M. et al. Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease. N. Engl. J. Med. 332, 413–418 (1995).

    Article  CAS  Google Scholar 

  14. Power, C. & Elliott, J. Cohort profile: 1958 British birth cohort (National Child Development Study). Int. J. Epidemiol. 35, 34–41 (2006).

    Article  Google Scholar 

  15. Clayton, D.G. et al. Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat. Genet. 37, 1243–1246 (2005).

    Article  CAS  Google Scholar 

  16. Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

    Article  CAS  Google Scholar 

  17. Wellcome Trust Case-Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).

  18. Cabannes, E., Khan, G., Aillet, F., Jarrett, R.F. & Hay, R.T. Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha. Oncogene 18, 3063–3070 (1999).

    Article  CAS  Google Scholar 

  19. Emmerich, F. et al. Overexpression of IκBα without inhibition of NF-κB activity and mutations in the IκBα gene in Reed-Sternberg cells. Blood 94, 3129–3134 (1999).

    CAS  PubMed  Google Scholar 

  20. Schmitz, R. et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J. Exp. Med. 206, 981–989 (2009).

    Article  CAS  Google Scholar 

  21. Barth, T.F. et al. Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma. Blood 101, 3681–3686 (2003).

    Article  CAS  Google Scholar 

  22. Joos, S. et al. Hodgkin's lymphoma cell lines are characterized by frequent aberrations on chromosomes 2p and 9p including REL and JAK2. Int. J. Cancer 103, 489–495 (2003).

    Article  CAS  Google Scholar 

  23. Martin-Subero, J.I. et al. Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma. Blood 99, 1474–1477 (2002).

    Article  CAS  Google Scholar 

  24. Villeneuve, L., Rassart, E., Jolicoeur, P., Graham, M. & Adams, J.M. Proviral integration site Mis-1 in rat thymomas corresponds to the pvt-1 translocation breakpoint in murine plasmacytomas. Mol. Cell. Biol. 6, 1834–1837 (1986).

    Article  CAS  Google Scholar 

  25. Beck-Engeser, G.B. et al. Pvt1-encoded microRNAs in oncogenesis. Retrovirology 5, 4 (2008).

    Article  Google Scholar 

  26. Bakkus, M.H., Brakel-van Peer, K.M., Michiels, J.J., van 't Veer, M.B. & Benner, R. Amplification of the c-myc and the pvt-like region in human multiple myeloma. Oncogene 5, 1359–1364 (1990).

    CAS  PubMed  Google Scholar 

  27. Huppi, K., Siwarski, D., Skurla, R., Klinman, D. & Mushinski, J.F. Pvt-1 transcripts are found in normal tissues and are altered by reciprocal(6;15) translocations in mouse plasmacytomas. Proc. Natl. Acad. Sci. USA 87, 6964–6968 (1990).

    Article  CAS  Google Scholar 

  28. Storlazzi, C.T. et al. Identification of a commonly amplified 4.3 Mb region with overexpression of C8FW, but not MYC in MYC-containing double minutes in myeloid malignancies. Hum. Mol. Genet. 13, 1479–1485 (2004).

    Article  CAS  Google Scholar 

  29. Crowther-Swanepoel, D. et al. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nat. Genet. 42, 132–136 (2010).

    Article  CAS  Google Scholar 

  30. Gudmundsson, J. et al. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat. Genet. 39, 631–637 (2007).

    Article  CAS  Google Scholar 

  31. Easton, D.F. et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447, 1087–1093 (2007).

    Article  CAS  Google Scholar 

  32. Tomlinson, I. et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat. Genet. 39, 984–988 (2007).

    Article  CAS  Google Scholar 

  33. Yeager, M. et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat. Genet. 39, 645–649 (2007).

    Article  CAS  Google Scholar 

  34. Amundadottir, L.T. et al. A common variant associated with prostate cancer in European and African populations. Nat. Genet. 38, 652–658 (2006).

    Article  CAS  Google Scholar 

  35. Kiemeney, L.A. et al. Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat. Genet. 40, 1307–1312 (2008).

    Article  CAS  Google Scholar 

  36. Tuupanen, S. et al. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat. Genet. 41, 885–890 (2009).

    Article  CAS  Google Scholar 

  37. Pomerantz, M.M. et al. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat. Genet. 41, 882–884 (2009).

    Article  CAS  Google Scholar 

  38. Faumont, N. et al. c-Myc and Rel/NF-κB are the two master transcriptional systems activated in the latency III program of Epstein-Barr virus-immortalized B cells. J. Virol. 83, 5014–5027 (2009).

    Article  CAS  Google Scholar 

  39. Ho, I.C., Tai, T.S. & Pai, S.Y. GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat. Rev. Immunol. 9, 125–135 (2009).

    Article  CAS  Google Scholar 

  40. Li, J., Qian, C.N. & Zeng, Y.X. Regulatory T cells and EBV associated malignancies. Int. Immunopharmacol. 9, 590–592 (2009).

    Article  CAS  Google Scholar 

  41. Atayar, C. et al. Expression of the T-cell transcription factors, GATA-3 and T-bet, in the neoplastic cells of Hodgkin lymphomas. Am. J. Pathol. 166, 127–134 (2005).

    Article  CAS  Google Scholar 

  42. La Rosa, F.A., Pierce, J.W. & Sonenshein, G.E. Differential regulation of the c-myc oncogene promoter by the NF-κB rel family of transcription factors. Mol. Cell. Biol. 14, 1039–1044 (1994).

    Article  CAS  Google Scholar 

  43. Maurice, D., Hooper, J., Lang, G. & Weston, K. c-Myb regulates lineage choice in developing thymocytes via its target gene Gata3. EMBO J. 26, 3629–3640 (2007).

    Article  CAS  Google Scholar 

  44. Papaemmanuil, E. et al. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat. Genet. 41, 1006–1010 (2009).

    Article  CAS  Google Scholar 

  45. Jundt, F. et al. Loss of PU.1 expression is associated with defective immunoglobulin transcription in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease. Blood 99, 3060–3062 (2002).

    Article  CAS  Google Scholar 

  46. Hjalgrim, H. & Engels, E.A. Infectious aetiology of Hodgkin and non-Hodgkin lymphomas: a review of the epidemiological evidence. J. Intern. Med. 264, 537–548 (2008).

    Article  CAS  Google Scholar 

  47. Stranger, B.E. et al. Genome-wide associations of gene expression variation in humans. PLoS Genet. 1, e78 (2005).

    Article  Google Scholar 

  48. Stranger, B.E. et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315, 848–853 (2007).

    Article  CAS  Google Scholar 

  49. Alexander, F.E. et al. An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin's disease (HD): evidence for a specific association with EBV+ve HD in young adults. Int. J. Cancer 107, 298–302 (2003).

    Article  CAS  Google Scholar 

  50. Jarrett, R.F. et al. The Scotland and Newcastle epidemiological study of Hodgkin's disease: impact of histopathological review and EBV status on incidence estimates. J. Clin. Pathol. 56, 811–816 (2003).

    Article  CAS  Google Scholar 

  51. Willett, E.V., O'Connor, S., Smith, A.G. & Roman, E. Does smoking or alcohol modify the risk of Epstein-Barr virus-positive or -negative Hodgkin lymphoma? Epidemiology 18, 130–136 (2007).

    Article  Google Scholar 

  52. Penegar, S. et al. National study of colorectal cancer genetics. Br. J. Cancer 97, 1305–1309 (2007).

    Article  CAS  Google Scholar 

  53. Hjalgrim, H. et al. Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. Cancer Res. 67, 2382–2388 (2007).

    Article  CAS  Google Scholar 

  54. Smedby, K.E. et al. Ultraviolet radiation exposure and risk of malignant lymphomas. J. Natl. Cancer Inst. 97, 199–209 (2005).

    Article  Google Scholar 

  55. Sorensen, K.M. et al. Whole genome amplification on DNA from filter paper blood spot samples: an evaluation of selected systems. Genet. Test. 11, 65–71 (2007).

    Article  CAS  Google Scholar 

  56. van Leeuwen, F.E. et al. Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin's disease. J. Natl. Cancer Inst. 95, 971–980 (2003).

    Article  Google Scholar 

  57. Broeks, A. et al. Increased risk of breast cancer following irradiation for Hodgkin's disease is not a result of ATM germline mutations. Int. J. Radiat. Biol. 76, 693–698 (2000).

    Article  CAS  Google Scholar 

  58. De Bruin, M.L. et al. Breast cancer risk in female survivors of Hodgkin's lymphoma: lower risk after smaller radiation volumes. J. Clin. Oncol. 27, 4239–4246 (2009).

    Article  Google Scholar 

  59. Lake, A. et al. Mutations of NFKBIA, encoding IκBα, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases. Int. J. Cancer 125, 1334–1342 (2009).

    Article  CAS  Google Scholar 

  60. Pettiti, D. Meta-analysis Decision Analysis and Cost-Effectiveness Analysis (Oxford University Press, Oxford, New York, 1994).

  61. Higgins, J.P. & Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med. 21, 1539–1558 (2002).

    Article  Google Scholar 

  62. Myers, S., Bottolo, L., Freeman, C., McVean, G. & Donnelly, P. A fine-scale map of recombination rates and hotspots across the human genome. Science 310, 321–324 (2005).

    Article  CAS  Google Scholar 

  63. Gabriel, S.B. et al. The structure of haplotype blocks in the human genome. Science 296, 2225–2229 (2002).

    Article  CAS  Google Scholar 

  64. Matys, V. et al. TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res. 34, D108–D110 (2006).

    Article  CAS  Google Scholar 

  65. Ferretti, V. et al. PReMod: a database of genome-wide mammalian cis-regulatory module predictions. Nucleic Acids Res. 35, D122–D126 (2007).

    Article  CAS  Google Scholar 

  66. Hallikas, O. et al. Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity. Cell 124, 47–59 (2006).

    Article  CAS  Google Scholar 

  67. Cuzick, J. Wilcoxon-type test for trend. Stat. Med. 4, 87–90 (1985).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Leukemia Lymphoma Research (UK) and Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) provided principal funding for the study. We acknowledge National Health Service (NHS) funding to the National Institute for Health Research (NIHR) Biomedical Research Centre. This study made use of control genotyping data generated by the Wellcome Trust Case Control Consortium. We acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, which was funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under awards 076113 and 085475. At the Institute of Cancer Research, sample and data acquisition was supported by Breakthrough Breast Cancer and the European Union, and we acknowledge NHS funding to the NIHR Biomedical Research Centre. We are grateful to the patients and their clinicians who participated in this collection (Supplementary Note). Work at the Leukaemia Research Fund (LRF) Virus Centre was funded by Leukaemia and Lymphoma Research. Sample and data acquisition for the UK replication series was also supported by the Kay Kendall Leukaemia Fund. The Epidemiology and Genetics Lymphoma Case-Control Study (ELCCS) was funded by Leukaemia and Lymphoma Research. Grant support to the German Study Group was through Deutsche Krebshilfe and the EU, grant HEALTH-F4-2007-200767. The SCALE study is supported by the Lundbeck Foundation grant R19 A2364, the Danish Cancer Research Foundation grant 41-08 and the Danish Cancer Society grant DP 08155. At the Department of Pathology and Medical Biology, University of Groningen, sample and data acquisition was supported by two grants from the Dutch Cancer Society (RUG 200-2315 and RUG 2009-4313). The Netherlands Cancer Institute (NKI) study was supported by the Dutch Cancer Society (grants No. NKI 98-1833, NKI 04-3068, NKI 08-3994) and the EU 6th framework programme (project no. 012926). We thank A. Kesminiene for coordinating the EU-framework project, M. Schaapveld and A. Eggermond for data management and L. Braaf and I. Mikolajewska for lab assistance. We are indebted to the patients and physicians who participated in this collection (Supplementary Note).

Author information

Author notes

  1. Victor Enciso-Mora, Peter Broderick and Yussanne Ma: These authors contributed equally to this work.

Authors and Affiliations

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

    Victor Enciso-Mora, Peter Broderick, Yussanne Ma, Bianca Olver, Amy Lloyd, Sara E Dobbins, Jayaram Vijayakrishnan & Richard S Houlston

  2. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

    Ruth F Jarrett, Lesley Shield, Annette Lake & Dorothy Montgomery

  3. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    Henrik Hjalgrim, Klaus Rostgaard & Mads Melbye

  4. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Kari Hemminki & Asta Försti

  5. Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden

    Kari Hemminki & Arjan Diepstra

  6. Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

    Anke van den Berg

  7. Department of Health Sciences, Epidemiology and Genetics Unit, University of York, York, UK

    Tracy Lightfoot & Eve Roman

  8. Department of Epidemiology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    Flora E van Leeuwen & Marieke de Bruin

  9. Department of Experimental Therapy, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    Annegien Broeks

  10. Department of Internal Medicine, University Hospital of Cologne, Cologne, Germany

    Andreas Engert, Elke Pogge von Strandmann & Katrin S Reiners

  11. Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

    Ilja M Nolte

  12. Department of Medicine, Unit of Clinical Epidemiology, Karolinska University Hospital, Stockholm, Sweden

    Karin E Smedby

  13. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Hans-Olov Adami

  14. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA

    Hans-Olov Adami

  15. Department of Radiotherapy, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    Nicola S Russell

  16. Department of Pathology and Oncology, Karolinska Institutet, Stockholm, Sweden

    Bengt Glimelius

  17. Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden

    Bengt Glimelius

  18. Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark

    Stephen Hamilton-Dutoit

  19. Department of Clinical Immunology, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark

    Lars P Ryder

  20. Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden

    Daniel Molin

  21. Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark

    Karina Meden Sorensen

  22. Cancer Prevention Institute of California, Fremont, California, USA

    Ellen T Chang & Anthony J Swerdlow

  23. Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA

    Ellen T Chang

  24. Cancer Immunogenetics Group, School of Cancer and Enabling Sciences, University of Manchester, Research Floor, St. Mary's Hospital, Manchester, UK

    Malcolm Taylor

  25. Section of Epidemiology, Institute of Cancer Research, Sutton, UK

    Rosie Cooke

  26. Department of Genetics University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

    Robert Hofstra & Helga Westers

  27. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

    Tom van Wezel & Ronald van Eijk

  28. The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK

    Alan Ashworth

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  1. Victor Enciso-Mora
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  2. Peter Broderick
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  45. Richard S Houlston
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Contributions

R.S.H. designed the study and obtained financial support. R.S.H. drafted the manuscript with contributions from P.B., V.E.-M., Y.M. and S.E.D. Y.M. and V.E.-M. performed statistical and bioinformatic analyses. P.B. performed sample coordination and laboratory analyses. B.O., Amy Lloyd and J.V. performed genotyping. A.J.S., A.A. and R.C. provided samples and data from a study conducted at the Institute of Cancer Research. E.R. initiated ELCCS. T.L., M.T. and E.R. managed and prepared Epidemiology and Genetics Lymphoma Case-Control Study samples. R.F.J. designed and conducted studies contributing to the UK replication series, and R.F.J., L.S., Annette Lake and Dorothy Montgomery prepared samples and collated data. F.E.v.L. designed the Dutch NKI study and obtained financial support. N.S.R. and M.d.B. were involved in identification and inclusion of Dutch cases, study design, review board approval and clinical implementation. A.B. coordinated collection and preparation of the NKI samples. A.F., K.H., A.E., E.P.v.S. and K.S.R. provided samples and data from German cases and controls. A.D., I.M.N. and A.v.d.B. collected samples and data from cHL cases ascertained through Groningen University. R.H., H.W., T.v.W. and R.v.E. performed ascertainment and collection of control samples from The Netherlands. H.H., M.M., K.R., L.P.R., K.E.S., H.-O.A., B.G., Daniel Molin, S.H.-D., K.M.S. and E.T.C. provided samples and data from the SCALE study in Denmark and Sweden. S.H.-D. analyzed samples and provided data from Danish cHL cases. All authors contributed to the final paper. R.F.J. and H.H. contributed equally to the paper and should be considered to have equal positional status in the author list.

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Correspondence to Richard S Houlston.

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Enciso-Mora, V., Broderick, P., Ma, Y. et al. A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3). Nat Genet 42, 1126–1130 (2010). https://doi.org/10.1038/ng.696

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