Brief Communication abstract

Nature Genetics 40, 26 - 28 (2008)
Published online: 16 December 2007 | doi:10.1038/ng.2007.41

Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk

Emma Jaeger1,17, Emily Webb2,17, Kimberley Howarth1,17, Luis Carvajal-Carmona1,3,17, Andrew Rowan1,17, Peter Broderick2,17, Axel Walther1,17, Sarah Spain1,17, Alan Pittman2,17, Zoe Kemp1, Kate Sullivan2, Karl Heinimann1,4, Steven Lubbe2, Enric Domingo1, Ella Barclay1, Lynn Martin1,5,6, Maggie Gorman1, Ian Chandler2, Jayaram Vijayakrishnan2, Wendy Wood2, Elli Papaemmanuil2, Steven Penegar2, Mobshra Qureshi2, members of the CORGI Consortium16, Susan Farrington7, Albert Tenesa8, Jean-Baptiste Cazier9, David Kerr10, Richard Gray11, Julian Peto12,13,14, Malcolm Dunlop7, Harry Campbell8, Huw Thomas15, Richard Houlston2 & Ian Tomlinson1,3

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We mapped a high-penetrance gene (CRAC1; also known as HMPS) associated with colorectal cancer (CRC) in the Ashkenazi population to a 0.6-Mb region on chromosome 15 containing SCG5 (also known as SGNE1), GREM1 and FMN1. We hypothesized that the CRAC1 locus harbored low-penetrance variants that increased CRC risk in the general population. In a large series of colorectal cancer cases and controls, SNPs near GREM1 and SCG5 were strongly associated with increased CRC risk (for rs4779584, P = 4.44 times 10- 14).

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  1. Molecular and Population Genetics Laboratory, Cancer Research UK, London WC2A 3PX, UK.
  2. Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, UK.
  3. Institute of Cancer, Bart's and the London Medical School, Queen Mary College, University of London, London EC1M 6BQ, UK.
  4. Research Group Human Genetics, Department of Clinical and Biological Sciences (KBW) Center for Biomedicine, Mattenstrasse 28, 4058 Basel, Switzerland.
  5. Department of Medical Genetics, St. Mary's Hospital, Manchester M13 0JH, UK.
  6. Department of Medical Genetics, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, UK.
  7. Colon Cancer Genetics Group, University of Edinburgh Cancer Research Centre and UK Medical Research Council (MRC) Human Genetics Unit, Western General Hospital, Edinburgh UK EH4 2XU, UK.
  8. Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
  9. Bioinformatics and Biostatistics, Cancer Research UK, London WC2A 3PX, UK.
  10. Department of Clinical Pharmacology, Oxford University, Radcliffe Infirmary, Oxford OX2 6HA, UK.
  11. Birmingham Clinical Trials Unit, University of Birmingham, Birmingham B15 2TT, UK.
  12. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK.
  13. Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
  14. Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
  15. Family Cancer Clinic and Imperial College, St Mark's Hospital, Harrow HA1 3UJ, UK.
  16. A full list of consortium members is provided in Supplementary Note online.
  17. These authors contributed equally to this work.

Correspondence to: Ian Tomlinson1,3 e-mail: ian.tomlinson@cancer.org.uk

Correspondence to: Richard Houlston2 e-mail: richard.houlston@icr.ac.uk



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