A common variant associated with prostate cancer in European and African populations

Laufey T Amundadottir^1, 12, Patrick Sulem^1, 12, Julius Gudmundsson^1, 12, Agnar Helgason¹, Adam Baker¹, Bjarni A Agnarsson², Asgeir Sigurdsson¹, Kristrun R Benediktsdottir², Jean-Baptiste Cazier¹, Jesus Sainz¹, Margret Jakobsdottir¹, Jelena Kostic¹, Droplaug N Magnusdottir¹, Shyamali Ghosh¹, Kari Agnarsson¹, Birgitta Birgisdottir¹, Louise Le Roux¹, Adalheidur Olafsdottir¹, Thorarinn Blondal¹, Margret Andresdottir¹, Olafia Svandis Gretarsdottir¹, Jon T Bergthorsson¹, Daniel Gudbjartsson¹, Arnaldur Gylfason¹, Gudmar Thorleifsson¹, Andrei Manolescu¹, Kristleifur Kristjansson¹, Gudmundur Geirsson³, Helgi Isaksson², Julie Douglas⁴, Jan-Erik Johansson⁵, Katarina Bälter⁶, Fredrik Wiklund⁶, James E Montie⁷, Xiaoying Yu⁸, Brian K Suarez⁹, Carole Ober¹⁰, Kathleen A Cooney^7, 11, Henrik Gronberg⁶, William J Catalona⁸, Gudmundur V Einarsson³, Rosa B Barkardottir², Jeffrey R Gulcher¹, Augustine Kong¹, Unnur Thorsteinsdottir¹ & Kari Stefansson¹

¹  deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.

²  Department of Pathology, Landspitali-University Hospital of Iceland, 101 Reykjavik, Iceland.

³  Department of Urology, Landspitali-University Hospital of Iceland, 101 Reykjavik, Iceland.

⁴  Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.

⁵  Department of Urology and Clinical Medicine, Örebro University Hospital, Sweden.

⁶  Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-17177 Stockholm, Sweden.

⁷  Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA.

⁸  Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

⁹  Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

¹⁰  Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.

¹¹  Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

¹²  These authors contributed equally to this work.

With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 10^-11). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.

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