Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21 (original) (raw)

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• 13 April 2008

In the version of this article initially published online, one of the co-authors (Kimberley Howarth) was inadvertently omitted from the author list. Her name should have been listed immediately after Zoe Kemp, with affiliation 18. This error has been corrected in all versions of the article.

References

1. Lichtenstein, P. et al. Environmental and heritable factors in the causation of cancer – Analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 343, 78–85 (2000).
   Article CAS Google Scholar
2. Barnetson, R.A. et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N. Engl. J. Med. 354, 2751–2763 (2006).
   Article CAS Google Scholar
3. Tenesa, A. et al. Association of MUTYH and colorectal cancer. Br. J. Cancer 95, 239–242 (2006).
   Article CAS Google Scholar
4. Zanke, B.W. et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat. Genet. 39, 989–994 (2007).
   Article CAS Google Scholar
5. 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
6. Haiman, C.A. et al. A common genetic risk factor for colorectal and prostate cancer. Nat. Genet. 39, 954–956 (2007).
   Article CAS Google Scholar
7. Broderick, P. et al. A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nat. Genet. 39, 1315–1317 (2007).
   Article CAS Google Scholar
8. Sokal, R.R. & Rohlf, F.J. Biometry: the Principles and Practice of Statistics in Biological Research 3rd edn (W.H. Freeman and Co., New York, 1995).
   Google Scholar
9. Churchill, G.A. & Doerge, R.W. Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971 (1994).
   CAS PubMed PubMed Central Google Scholar
10. Storey, J.D. & Tibshirani, R. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA 100, 9440–9445 (2003).
    Article CAS Google Scholar
11. Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906–913 (2007).
    Article CAS Google Scholar
12. Wray, N.R., Goddard, M.E. & Visscher, P.M. Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res. 17, 1520–1528 (2007).
    Article CAS Google Scholar
13. Skol, A.D., Scott, L.J., Abecasis, G.R. & Boehnke, M. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat. Genet. 38, 209–213 (2006).
    Article CAS Google Scholar
14. Tenesa, A. & Dunlop, M.G. Validity of tagging SNPs across populations for association studies. Eur. J. Hum. Genet. 14, 357–363 (2006).
    Article CAS Google Scholar
15. Barrett, J.C., Fry, B., Maller, J. & Daly, M.J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265 (2005).
    Article CAS Google Scholar
16. Farrington, S.M. et al. Germline susceptibility to colorectal cancer due to base-excision repair gene defects. Am. J. Hum. Genet. 77, 112–119 (2005).
    Article CAS Google Scholar

Download references

Acknowledgements

Edinburgh: We are grateful to all participants in these studies and to nursing and administrative staff on the COGS and SOCCS studies. We acknowledge the working arrangements with the Genotyping Core at the Wellcome Trust Clinical Research Facility, managed by L. Murphy, for sample preparations and genotyping (COGS, SOCCS, Scotland replication and LBC 1936 samples). We also thank departments in central Scottish NHS, including Cancer Registry, Scottish Cancer Intelligence Unit of ISD and the Family Practitioner Committee for population control recruitment. The work was funded by grants from Cancer Research UK (C348/A3758 and A8896, C48/A6361), Medical Research Council (G0000657-53203) and Scottish Executive Chief Scientist's Office (K/OPR/2/2/D333, CZB/4/449), and a Centre Grant from CORE as part of the Digestive Cancer Campaign. J.P. was funded by an MRC PhD studentship. Research work at the Edinburgh Parallel Computing Centre was supported by the Scottish Funding Council through the 'e-Science Data, Information and Knowledge Transformation 2' (eDIKT2) project (SFC grant HR04019). The Lothian Birth Cohort 1936 phenotype and DNA collection was supported by Programme Grant number 251 and the Sidney De Haan Research Award from Research Into Ageing, and by the Disconnected Mind Award from Help the Aged. I.J.D. holds a Royal Society-Wolfson Research Merit Award. Sample collection, DNA extraction and phenotype data were collected at the Wellcome Trust Clinical Research Facility, Edinburgh. Cambridge: We thank the SEARCH study team and all the participants in the study. P.D.P.P. is a Cancer Research UK Senior Clinical Research Fellow. T.K. is funded by the Foundation Dr Henri Dubois-Ferriere Dinu Lipatti. Kiel: The study was supported by the German National Genome Research Network (NGFN) through the POPGEN biobank (BmBF 01GR0468) and the National Genotyping Platform. Further support was obtained through the MediGrid and Services@MediGrid projects (01AK803G and 01IG07015B). SHIP is part of the Community Medicine Research net (CMR) of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grant no. ZZ9603), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Heidelberg: We wish to thank all participants and the staff of the participating clinics for their contribution to the data collection and B.Kaspereit, K. Smit and U. Eilber in the Division of Cancer Epidemiology, and U. Handte-Daub, S. Toth and B. Collins in the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center for their excellent technical assistance. This study was supported by the German Research Council (Deutsche Forschungsgemeinschaft), grant numbers BR 1704/6-1, BR 1704/6-3 and CH 117/1-1, and by the German Federal Ministry for Education and Research, grant number 01 KH 0404. Barcelona: The Bellvitge Colorectal Cancer Study has been funded by the Spanish Instituto de Salud Carlos III, FIS (grants 97/0787, 03/0114 and 05/1006), Ministry of Science and Education (SAF 06/06084) and Acción Transversal del Cáncer 2008. London: We acknowledge Cancer Research UK Research funding and thank all those who participated in this study. Michigan: Genotyping of Michigan samples was supported by NCI R01 CA81488, the Irving Weinstein Foundation and the University of Michigan Comprehensive Cancer Center Core Grant, P30 CA46592. Tokyo: We thank members of the Rotary Club of Osaka Midosuji District (Japan) for collecting samples, and M. Kubo (RIKEN, Japan) for SNP genotyping. The study was supported by 'Biobank Japan', a project working toward personalized medicine. Canada: We gratefully acknowledge the contribution of A. Belisle, V. Catudal and R. Fréchette. Cancer Care Ontario, as the host organization to the ARCTIC Genome Project, acknowledges that this project was funded by Genome Canada through the Ontario Genomics Institute, by Génome Québec, the Ministère du Dévelopement Économique et Régional et de la Recherche du Québec and the Ontario Institute for Cancer Research (B.W.Z., T.J.H., C.M.T.G. and S.G.). Additional funding was provided by the National Cancer Institute of Canada (NCIC) through the Cancer Risk Assessment (CaRE) Program Project Grant. The work was supported through collaboration and cooperative agreements with the Colon Cancer Family Registry and PIs, supported by the National Cancer Institute, National Institutes of Health under RFA CA-95-011, including the Ontario Registry for Studies of Familial Colorectal Cancer (S.G.) (U01 CA076783). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating institutions or investigators in the Colon CFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the Colon CFR.

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Author notes

1. Albert Tenesa and Susan M Farrington: These authors contributed equally to this work.

Authors and Affiliations

1. Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, EH4 2XU, Edinburgh, UK
   Albert Tenesa, Susan M Farrington, James G D Prendergast, Marion Walker, Naila Haq, Rebecca A Barnetson, Evropi Theodoratou, Nicola Cartwright, Colin Semple, Andrew J Clark, Harry Campbell & Malcolm G Dunlop
2. Clinical Genetics Department, Western General Hospital, EH4 2XU, Edinburgh, UK
   Mary E Porteous & Roseanne Cetnarskyj
3. Public Health Sciences, University of Edinburgh, EH8 9AG, Edinburgh, UK
   Evropi Theodoratou & Harry Campbell
4. Edinburgh Parallel Computing Centre, University of Edinburgh, EH9 3JZ, Edinburgh, UK
   Fiona J L Reid, Lorna A Smith & Kostas Kavoussanakis
5. Department of Oncology, Cancer Research UK Laboratories, University of Cambridge, CB1 8RN, Cambridge, UK
   Thibaud Koessler & Paul D P Pharoah
6. Department of General Internal Medicine University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstraße 12, 24105, Kiel, Germany
   Stephan Buch, Jürgen Tepel & Jochen Hampe
7. POPGEN Biobank, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstraße 12, 24105, Kiel, Germany
   Stephan Buch, Clemens Schafmayer & Stefan Schreiber
8. Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Germany
   Clemens Schafmayer & Jürgen Tepel
9. Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstraße 12, 24105, Kiel, Germany
   Stefan Schreiber
10. Institute for Community Medicine, University Hospital Greifswald, Walther Rathenau Str. 48, 17487, Greifswald, Germany
    Henry Völzke & Carsten O Schmidt
11. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
    Jenny Chang-Claude
12. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
    Michael Hoffmeister & Hermann Brenner
13. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
    Stefan Wilkening & Federico Canzian
14. Translational Research Laboratory, IDIBELL-Catalan Institute of Oncology and University of Barcelona, L 'Hospitalet, 08907, Barcelona, Spain
    Gabriel Capella
15. Bioinformatics Unit, IDIBELL-Catalan Institute of Oncology and University of Barcelona, L 'Hospitalet, 08907, Barcelona, Spain
    Victor Moreno
16. Department of Psychology, University of Edinburgh, EH8 9JZ, Edinburgh, UK
    Ian J Deary
17. Geriatric Medicine, University of Edinburgh, Royal Victoria Hospital, EH4 2DN, Edinburgh, UK
    John M Starr
18. Molecular and Population Genetics Laboratory, Cancer Research UK London Research Institute, WC2A 3PX, London, UK
    Ian P M Tomlinson, Zoe Kemp, Kimberley Howarth, Luis Carvajal-Carmona & Jagadish Rangrej
19. Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, UK
    Emily Webb, Peter Broderick, Jayaram Vijayakrishnan & Richard S Houlston
20. CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion x2013 Israel Institute of Technology, Haifa, Israel
    Gad Rennert
21. Perlegen Sciences, Mountain View, 94043, California, USA
    Dennis Ballinger
22. Departments of Internal Medicine, Epidemiology and Human Genetics, University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA
    Laura Rozek & Stephen B Gruber
23. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 108-8639, Tokyo, Japan
    Koichi Matsuda, Tomohide Kidokoro & Yusuke Nakamura
24. Cancer Care Ontario, 620 University Avenue, Toronto, M5G 1L7, Ontario, Canada
    Brent W Zanke, Celia M T Greenwood, Rafal Kustra, Thomas J Hudson & Steven Gallinger
25. Ontario Institute for Cancer Research, 101 College Street, Toronto, M5G 2L7, Ontario, Canada
    Brent W Zanke & Thomas J Hudson
26. Division of Hematology, The University of Ottawa, Faculty of Medicine, 501 Smythe Road, K1H 8L6, Ottawa, Canada
    Brent W Zanke
27. Genetics and Genome Biology, Hospital for Sick Children, 15-703 TMDT East, 101 College Street, Toronto, M5G 1L7, Ontario, Canada
    Celia M T Greenwood & Jagadish Rangrej
28. Department of Public Health Sciences, University of Toronto, Health Sciences Building, 155 College Street, Toronto, M5T 3M7, Ontario, Canada
    Celia M T Greenwood
29. The McGill University and Genome Quebec Innovation Centre, 700 Dr. Penfield Ave., Montreal, H3G 1A4, Quebec, Canada
    Alexandre Montpetit
30. Samuel Lunenfeld Research Institute, Mount Sinai Hospital and University of Toronto, 600 University Avenue, Toronto, M5G 1X5, Ontario, Canada
    Steven Gallinger

Authors

1. Albert Tenesa
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2. Susan M Farrington
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3. James G D Prendergast
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4. Mary E Porteous
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5. Marion Walker
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6. Naila Haq
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7. Rebecca A Barnetson
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8. Evropi Theodoratou
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9. Roseanne Cetnarskyj
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10. Nicola Cartwright
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11. Colin Semple
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12. Andrew J Clark
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13. Fiona J L Reid
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14. Lorna A Smith
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15. Kostas Kavoussanakis
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16. Thibaud Koessler
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17. Paul D P Pharoah
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18. Stephan Buch
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19. Clemens Schafmayer
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20. Jürgen Tepel
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21. Stefan Schreiber
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22. Henry Völzke
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23. Carsten O Schmidt
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24. Jochen Hampe
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25. Jenny Chang-Claude
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26. Michael Hoffmeister
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27. Hermann Brenner
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28. Stefan Wilkening
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29. Federico Canzian
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30. Gabriel Capella
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31. Victor Moreno
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32. Ian J Deary
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33. John M Starr
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34. Ian P M Tomlinson
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35. Zoe Kemp
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36. Kimberley Howarth
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37. Luis Carvajal-Carmona
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38. Emily Webb
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39. Peter Broderick
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40. Jayaram Vijayakrishnan
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41. Richard S Houlston
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42. Gad Rennert
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43. Dennis Ballinger
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44. Laura Rozek
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45. Stephen B Gruber
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46. Koichi Matsuda
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47. Tomohide Kidokoro
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48. Yusuke Nakamura
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49. Brent W Zanke
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50. Celia M T Greenwood
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51. Jagadish Rangrej
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52. Rafal Kustra
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53. Alexandre Montpetit
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54. Thomas J Hudson
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55. Steven Gallinger
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56. Harry Campbell
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57. Malcolm G Dunlop
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Contributions

M.G.D. conceived of the study; A.T., S.M.F., H.C. and M.G.D. designed it; A.T., S.M.F., H.C. and M.G.D. wrote the paper with input from other authors; A.T., S.M.F., J.G.D.P. and C. Semple undertook data manipulations, statistical analysis and bioinformatic interrogations; S.M.F., M.W., N.H., R.A.B., A.J.C. undertook various aspects of laboratory analysis; M.E.P., E.T., R.C., N.C. and A.J.C. coordinated and/or undertook recruitment, collected phenotype data, undertook related data handling and curation, managed recruitment, obtained biological samples; F.J.L.R., L.A.S. and K.K. contributed to writing code in EPCC and parallelized the analysis for permutation testing. The following authors from the various collaborating groups conceived the local study, undertook assembly of case/control series in their respective regions, collected data and samples, variously undertook genotyping and analysis: T. Koessler and P.D.P.P. in Cambridge; S.B., C. Schafmayer, J.T., S.S., H.V., C.O.S. and J.H. in Kiel; J.C.-C., M.H. and H.B. in Heidelberg; S.W. and F.C. in Heidelberg; G.C. and V.M. in Barcelona; I.J.D. and J.M.S. in Edinburgh; I.P.M.T., Z.K. and L.C.-C. in London LRF; E.W., P.B., J.V. and R.S.H. in London ICR; G.R., D.B., L.R., S.B.G. in Michigan/Haifa; K.M., T. Kidokoro and Y.N. in Tokyo; B.W.Z., C.M.T.G., J.R., R.K., A.M., T.J.H. and S.G. in Toronto and Quebec. All undertook sample collection and phenotype data collection and collation in the respective centres. M.G.D., H.C., I.P.M.T. and R.S.H. obtained funding for the study.

Corresponding author

Correspondence toMalcolm G Dunlop.

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Competing interests

Dennis Ballinger is employed by Perlegen Sciences, which undertakes whole genome genetic analysis commercially. Brent Zanke is founder and equity holder of Arctic Dx, a new Canadian biotechnology company that has received a license in the field of diagnostics for intellectual property generated by several institutions in Canada and other countries.

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Tenesa, A., Farrington, S., Prendergast, J. et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.Nat Genet 40, 631–637 (2008). https://doi.org/10.1038/ng.133

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• Received: 05 December 2007
• Accepted: 29 February 2008
• Published: 30 March 2008
• Issue Date: May 2008
• DOI: https://doi.org/10.1038/ng.133