Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 10^-13; heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13–1.41; homozygote OR: 1.58, 95% c.i.: 1.40–1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 10^-11; rs6983267 P = 6.62 10^-10). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).

1. SAIC-Frederick, National Cancer Institute (NCI)-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
2. Division of Cancer Epidemiology and Genetics, Center for Cancer Research, NCI, US National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland 20892, USA.
3. Pediatric Oncology Branch, Center for Cancer Research, NCI, US National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland 20892, USA.
4. Bioinformed Consulting Services, Gaithersburg, Maryland 20877, USA.
5. Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
6. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
7. Department of Mathematics and Statistics, Lancaster University, Lancaster LA1 4YF, UK.
8. Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia 30329, USA.
9. Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, FIN-00300, Finland.
10. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
11. Centre de Recherche pour les Pathologies Prostatiques (CeRePP), Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75970 Paris, France.
12. Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
13. Division of Hematology and Oncology, Columbia University, New York, New York 10032, USA.
14. Office of Cancer Genomics, NCI, NIH, DHHS, Bethesda, Maryland 20892, USA.

Correspondence to: Stephen J Chanock^2,3 e-mail: chanocks@mail.nih.gov

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