Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions¹, with African American men having among the highest worldwide incidence and mortality rates². Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered³, accounts for about 11%–13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%–4%) susceptibility variant in individuals of European descent that happens to be very common (42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

1. deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
2. Department of Pathology, Landspitali-University Hospital, 101 Reykjavik, Iceland.
3. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
4. Division of Medical Oncology, Lozano Blesa University Hospital, University of Zaragoza, 50009 Zaragoza, Spain.
5. Department of Urology, Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21209, USA.
6. Thrombosis Service, 6503 GM Nijmegen, The Netherlands.
7. The Institute of Health Sciences, Nanotechnology Institute of Aragon, 50009 Zaragoza, Spain.
8. Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
9. Division of Radiation Oncology, University Hospital, Zaragoza, Spain.
10. Comprehensive Cancer Center East, 6501 BG Nijmegen, The Netherlands, and Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
11. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
12. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
13. Department of Urology, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
14. Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
15. Department of Urology, Landspitali-University Hospital, 101 Reykjavik, Iceland.
16. Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
17. These authors contributed equally to this work.

Correspondence to: Kari Stefansson¹ e-mail: kstefans@decode.is

Correspondence to: Augustine Kong¹ e-mail: augustine.kong@decode.is

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