Sequence variants at the TERT-CLPTM1L locus associate with many cancer types (original) (raw)

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Acknowledgements

We thank the individuals that participated in the study and whose contribution made this work possible. We also thank the nurses at deCODE's participant recruitment center and the personnel at deCODE's core facilities. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the Icelandic subjects with cancer. The project was funded in part by the European Commission (POLYGENE: LSHC-CT-2005-018827 and GENADDICT: LSHM-CT-2004-005166), the National Institutes of Health (R01-DA017932) and a research investment grant of the Radboud University Nijmegen Medical Centre. The Leeds Bladder Cancer Study was funded by Cancer Research UK and Yorkshire Cancer Research. Torino Bladder Cancer Case Control Study was supported by a grant to ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No 513943); and by a grant of the compagnia di San Paolo, the Italian Association for Cancer Research, Italy and the Piedmont Region Progetti di Ricerca Sanitaria Finalizzata. J.H. is supported by the Swedish Cancer Society, The Radiumhemmet Research Funds, The Swedish Research Council and the Karolinska Institutet Research Funds.

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1. Thorunn Rafnar and Patrick Sulem: These authors contributed equally to this work.

Authors and Affiliations

1. deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
   Thorunn Rafnar, Patrick Sulem, Simon N Stacey, Frank Geller, Julius Gudmundsson, Asgeir Sigurdsson, Margret Jakobsdottir, Hafdis Helgadottir, Steinunn Thorlacius, Thorarinn Blöndal, Thorgeir E Thorgeirsson, Gudmar Thorleifsson, Kristleifur Kristjansson, Hjordis Bjarnason, Margret Asgeirsdottir, Kari T Kristinsson, Sigurborg Matthiasdottir, Michael L Frigge, Jeffrey R Gulcher, Gisli Masson, Daniel F Gudbjartsson, Augustine Kong, Unnur Thorsteinsdottir & Kari Stefansson
2. Comprehensive Cancer Center East, BG, 6501, Nijmegen, The Netherlands
   Katja K H Aben & Lambertus A Kiemeney
3. Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, HB, 6500, Nijmegen, The Netherlands
   Katja K H Aben, Femmie de Vegt & Lambertus A Kiemeney
4. Department of Dermatology, University of Iceland, 101 Reykjavik, Iceland
   Kristin Thorisdottir, Bardur Sigurgeirsson & Jon H Olafsson
5. Departments of Plastic Surgery, Landspitali-University Hospital, 101 Reykjavik, Iceland
   Rafn Ragnarsson
6. Medical Oncology, Landspitali-University Hospital, 101 Reykjavik, Iceland
   Halla Skuladottir
7. Surgery, Landspitali-University Hospital, 101 Reykjavik, Iceland
   Tomas Gudbjartsson & Thorvaldur Jonsson
8. Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
   Tomas Gudbjartsson, Kristrun R Benediktsdottir, Bjarni A Agnarsson, Thorvaldur Jonsson, Steinn Jonsson, Jon H Olafsson, Unnur Thorsteinsdottir & Kari Stefansson
9. Departments of Pathology, Landspitali-University Hospital, 101 Reykjavik, Iceland
   Helgi J Isaksson, Kristrun R Benediktsdottir, Bjarni A Agnarsson & Rosa B Barkardottir
10. Urology, Landspitali-University Hospital, 101 Reykjavik, Iceland
    Gudmundur V Einarsson & Eirikur Jonsson
11. Obstetrics and Gynecology, Landspitali-University Hospital, 101 Reykjavik, Iceland
    Karl Olafsson, Anna Salvarsdottir & Hafsteinn Saemundsson
12. Clinical Research Centre, Krokhals 5D, 110 Reykjavik, Iceland
    Steinunn G Sveinsdottir
13. ISI Foundation (Institute for Scientific Interchange), Torino, 10133, Italy
    Silvia Polidoro, Giuseppe Matullo & Paolo Vineis
14. Department of Genetics, Biology and Biochemistry, University of Torino, Torino, 10126, Italy
    Silvia Polidoro & Giuseppe Matullo
15. Department of Oncology-Pathology, Cancer Centre Karolinska, Karolinska Institutet, Karolinska University Hospital Solna Stockholm, S-171 76, Sweden
    Veronica Höiom, Gunnar Steineck & Johan Hansson
16. Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, 46009, Spain
    Rafael Botella-Estrada & Eduardo Nagore
17. Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, D-69120, Germany
    Kari Hemminki & Rajiv Kumar
18. National Institute of Environmental Health, Budapest, H-1450, Hungary
    Peter Rudnai
19. Section of Epidemiology & Biostatistics, Leeds Institute of Molecular Medicine, St. James's University Hospital, LS9 7TF, Leeds, UK
    D Timothy Bishop
20. Department of Experimental and Applied Medicine - Section of Occupational Medicine and Industrial Hygiene, University of Brescia, Brescia, 25125, Italy
    Marcello Campagna & Stefano Porru
21. Department of General Practice, Catholic University of Leuven, Leuven, 3000, Belgium
    Eliane Kellen & Frank Buntinx
22. Leuven University Centre for Cancer Prevention (LUCK), Leuven, 3000, Belgium
    Eliane Kellen
23. Department of Public Health and Epidemiology, Unit of Genetic Epidemiology, University of Birmingham, Birmingham, B15 2TT, UK
    Maurice P Zeegers
24. Department of Complex Genetics, Cluster of Genetics and Cell Biology, Nutrition and Toxicology Research Institute, Maastricht University, MD, 6200, Maastricht, The Netherlands
    Maurice P Zeegers
25. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, S171 76, Sweden
    Petra de Verdier & Annika Lindblom
26. Division of Medical Oncology, University Hospital, 50009, Zaragoza, Spain
    Ana Ferrer, Dolores Isla, Maria Jesus Vidal, Raquel Andres, Alejandro Tres & José I Mayordomo
27. Health Science Institute, Zaragoza, 50009, Spain
    Berta Saez
28. Division of Dermatology, University Hospital, Zaragoza, 50009, Spain
    Pablo Juberias
29. Divisions of Nuclear Medicine, University Hospital, Zaragoza, 50009, Spain
    Javier Banzo
30. Radiation Oncology, University Hospital, Zaragoza, 50009, Spain
    Sebastian Navarrete
31. Health Science Institute, Nanotechnology Institute of Aragon, Zaragoza, 50009, Spain
    Alejandro Tres & José I Mayordomo
32. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, 60611, Illinois, USA
    Donghui Kan & William J Catalona
33. Environmental Health Center, Cluj Napoca, 400166, Romania
    Eugene Gurzau
34. State Health Institute, SK-975 56 Banska Bystrica, Slovakia
    Kvetoslava Koppova
35. Departments of Urology, Radboud University Nijmegen Medical Centre, PO Box 9101, HB, 6500, Nijmegen, The Netherlands
    Jack A Schalken, Egbert Oosterwijk, Onno van Hooij & Lambertus A Kiemeney
36. Pulmonary Diseases, Radboud University Nijmegen Medical Centre, PO Box 9101, HB, 6500, Nijmegen, The Netherlands
    Henricus F M van der Heijden
37. Department of Pulmonary Medicine, Rijnstate Hospital, Arnhem, The Netherlands
    Hans J Smit
38. Department of Pulmonary Diseases, Canisius-Wilhelmina Hospital, Weg door Jonkerbos 100, Nijmegen, 6532 SZ, The Netherlands
    René A Termeer
39. Department of Oncology, Sahlgrenska University Hospital, Goteborg, S-413 45, Sweden
    Gunnar Steineck
40. Department of General Practice, Maastricht University, MD, 6200, Maastricht, The Netherlands
    Frank Buntinx
41. Department of Epidemiology and Public Health, Imperial College, London, W2 1PG, UK
    Paolo Vineis
42. Section of Experimental Oncology, Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds, LS9 7TF, UK
    Anne E Kiltie
43. Department of Medicine, Landspitali-University Hospital, Reykjavik, 101, Iceland
    Steinn Jonsson

Authors

1. Thorunn Rafnar
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2. Patrick Sulem
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3. Simon N Stacey
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4. Frank Geller
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5. Julius Gudmundsson
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6. Asgeir Sigurdsson
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7. Margret Jakobsdottir
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8. Hafdis Helgadottir
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9. Steinunn Thorlacius
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10. Katja K H Aben
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11. Thorarinn Blöndal
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12. Gudmar Thorleifsson
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13. Kristleifur Kristjansson
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14. Kristin Thorisdottir
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15. Halla Skuladottir
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16. Tomas Gudbjartsson
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17. Helgi J Isaksson
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18. Kristrun R Benediktsdottir
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19. Karl Olafsson
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20. Anna Salvarsdottir
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21. Hjordis Bjarnason
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22. Margret Asgeirsdottir
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23. Kari T Kristinsson
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24. Sigurborg Matthiasdottir
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25. Steinunn G Sveinsdottir
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26. Silvia Polidoro
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27. Veronica Höiom
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28. Rafael Botella-Estrada
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29. Kari Hemminki
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30. Peter Rudnai
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31. D Timothy Bishop
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32. Marcello Campagna
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33. Eliane Kellen
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34. Maurice P Zeegers
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35. Petra de Verdier
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36. Ana Ferrer
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37. Dolores Isla
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38. Maria Jesus Vidal
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39. Raquel Andres
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40. Berta Saez
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41. Pablo Juberias
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42. Javier Banzo
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43. Sebastian Navarrete
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44. Alejandro Tres
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45. Donghui Kan
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46. Annika Lindblom
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47. Eugene Gurzau
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48. Kvetoslava Koppova
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49. Femmie de Vegt
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50. Jack A Schalken
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51. Henricus F M van der Heijden
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52. Hans J Smit
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53. René A Termeer
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54. Egbert Oosterwijk
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55. Onno van Hooij
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57. Stefano Porru
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60. Frank Buntinx
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62. Giuseppe Matullo
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63. Paolo Vineis
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64. Anne E Kiltie
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65. José I Mayordomo
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66. Rajiv Kumar
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67. Lambertus A Kiemeney
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Contributions

The study was designed and results were interpreted by T.R., P.S., S.N.S., F.G., J.G., J.R.G., D.F.G., A.K., S.T., U.T. and K.S. Statistical analysis was carried out by P.S., F.G., D.F.G., M.L.F., G.T. and A.K. Subject ascertainment, recruitment, biological material collection and collection of clinical and lifestyle information was organized and carried out by T.E.T., K. Kristjansson, S.G.S., R.R., B. Sigurgeirsson, K.T., J.H.O., S.J., H.H., T.G., H.J.I., E.J., T.J., G.V.E., R.B.B., K.R.B., B.A.A., H. Skuladottir, K.O., A. Salvarsdottir, H. Saemundsson, J.H., V.H., E.N., S. Polidoro, S. Porru, R.B.-E., R.K., K.H., P.R., K. Koppova, E.G., G.S., D.T.B., A.E.K., M.C., E.K., M.P.Z., P.V., P.d.V., G. Matullo, A.F., D.I., M.J.V., R.A., B. Saez, P.J., J.B., S.N., A.T., D.K., A.L., F.d.V., F.B., W.J.C., J.A.S., H.F.M.v.d.H., H.J.S., R.A.T., E.O., O.v.H., K.K.H.A., J.I.M., L.A.K. Principal collaborators for the non-Icelandic populations were L.A.K. (The Netherlands), J.I.M. (Zaragoza, Spain), A.E.K. (UK), G. Matullo and P.V. (Torino), S.P. (Brescia), M.P.Z. and F.B. (Belgium), R.K. (Eastern Europe), G.S. (bladder cancer, Sweden), J.H. (melanoma, Sweden), E.N. (Valencia, Spain) and W.J.C. (Chicago, USA). Genotyping and laboratory experiments were carried out by A. Sigurdsson, T.B., M.J., H.H., H.B., M.A., K.T.K. and S.M. Bioinformatic analysis was carried out by P.S., T.R., A. Sigurdsson, T.E.T., G. Masson, T.B. and G.T. Authors T.R., P.S., D.F.G., A.K., U.T. and K.S. drafted the manuscript. All authors contributed to the final version of the paper.

Corresponding authors

Correspondence toThorunn Rafnar or Kari Stefansson.

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The authors from deCODE Genetics are shareholders in deCODE Genetics Inc. and therefore declare competing financial interest.

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Rafnar, T., Sulem, P., Stacey, S. et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.Nat Genet 41, 221–227 (2009). https://doi.org/10.1038/ng.296

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• Received: 28 October 2008
• Accepted: 05 November 2008
• Published: 18 January 2009
• Issue Date: February 2009
• DOI: https://doi.org/10.1038/ng.296