In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 10^{- 10}), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 10^{- 26}) and 18q21 (rs4939827; OR = 1.2; P = 7.8 10^{- 28}). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75–3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.

1. Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Edinburgh EH4 2XU, UK.
2. Clinical Genetics Department, Western General Hospital, Edinburgh EH4 2XU, UK.
3. Public Health Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK.
4. Edinburgh Parallel Computing Centre, University of Edinburgh, Edinburgh EH9 3JZ, UK.
5. Cancer Research UK Laboratories, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
6. Department of General Internal Medicine University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstrae 12, 24105 Kiel, Germany.
7. POPGEN Biobank, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstrae 12, 24105 Kiel, Germany.
8. Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, 24105 Kiel, Germany.
9. Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstrae 12, 24105 Kiel, Germany.
10. Institute for Community Medicine, University Hospital Greifswald, Walther Rathenau Str. 48, 17487 Greifswald, Germany.
11. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
12. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
13. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
14. Translational Research Laboratory, IDIBELL-Catalan Institute of Oncology and University of Barcelona, L 'Hospitalet, Barcelona 08907, Spain.
15. Bioinformatics Unit, IDIBELL-Catalan Institute of Oncology and University of Barcelona, L 'Hospitalet, Barcelona 08907, Spain.
16. Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
17. Geriatric Medicine, University of Edinburgh, Royal Victoria Hospital, Edinburgh EH4 2DN, UK.
18. Molecular and Population Genetics Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK.
19. Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, UK.
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.
21. Perlegen Sciences, Mountain View, California 94043, USA.
22. Departments of Internal Medicine, Epidemiology and Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
23. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
24. Cancer Care Ontario, 620 University Avenue, Toronto, Ontario M5G 1L7, Canada.
25. Ontario Institute for Cancer Research, 101 College Street, Toronto, Ontario M5G 2L7, Canada.
26. The University of Ottawa, Faculty of Medicine, Division of Hematology, 501 Smythe Road, Ottawa K1H 8L6, Canada.
27. Genetics and Genome Biology, Hospital for Sick Children, 15-703 TMDT East, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
28. University of Toronto, Department of Public Health Sciences, Health Sciences Building, 155 College Street, Toronto, Ontario M5T 3M7, Canada.
29. The McGill University and Genome Quebec Innovation Centre, 700 Dr. Penfield Ave., Montreal, Quebec H3G 1A4, Canada.
30. Samuel Lunenfeld Research Institute, Mount Sinai Hospital and University of Toronto, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
31. These authors contributed equally to this work.

Correspondence to: Malcolm G Dunlop¹ e-mail: Malcolm.Dunlop@hgu.mrc.ac.uk

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