Article abstract
Nature Genetics 40, 1426 - 1435 (2008)
Published online: 16 November 2008 | doi:10.1038/ng.262
Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer
COGENT Study1
Abstract
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 
10-10), 16q22.1 (rs9929218, CDH1; P = 1.2 10-8), 19q13.1 (rs10411210, RHPN2; P = 4.6 10-9) and 20p12.3 (rs961253; P = 2.0 10-10). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.
- A full list of authors and affiliations is provided at the end of this paper.
- Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, UK.
- Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
- Department of Clinical Pharmacology, Oxford University, Old Road Campus Research Building, Oxford, OX2 6HA, UK.
- Bioinformatics and Biostatistics, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
- Department of Medical Genetics, Genome-Scale Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
- Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Edinburgh EH4 2XU, UK.
- Clinical Genetics, Western General Hospital, Edinburgh EH4 2XU, UK.
- Cancer Research UK Laboratories, Strangeways Research Laboratory Department of Oncology, University of Cambridge, Cambridge, UK.
-
Department of General Internal Medicine, University Hospital, Schleswig-Holstein, Campus Kiel, Schittenhelmstra
e 12, 24105 Kiel, Germany. - POPGEN Biobank, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstrasse 12, 24105 Kiel, Germany.
- Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse, 24105 Kiel, Germany.
- Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstrasse 12, 24105 Kiel, Germany.
- Institut für Epidemiologie und Sozialmedizin, University Hospital Greifswald, Walther-Rathenau-Strasse 48 Greifswald 17487, Germany.
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
- The Ottawa Health Research Institute, Division of Epidemiology, 501 Smythe Road, Ottawa, Canada, K1H 8L6.
- The McGill University and Genome Quebec Innovation Centre, 740 Dr Penfield Avenue, Montreal Quebec, Canada H3G 1A4.
- Cancer Care Ontario, 620 University Avenue, Toronto Ontario M5G 1L7 and Ontario Institute for Cancer Research, 101 College Street, Toronto, Canada M5G 2L7.
- A full list of members is provided in the Supplementary Note online.
Correspondence to: e-mail: richard.houlston@icr.ac.uk
Correspondence to: e-mail: iant@well.ox.ac.uk
Correspondence to: e-mail: malcolm.dunlop@hgu.mrc.ac.uk
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