RESEARCH HIGHLIGHTS Nature Reviews Urology 11, 661 (2014); published online 30 September 2014; doi:10.1038/nrurol.2014.277

PROSTATE CANCER

A meta-analysis of nine genome-wide association studies (GWAS) involving men of diverse ancestries has identified 23 new prostate cancer susceptibility loci, taking the current total of known loci to 100, that between them explain 33% of familial risk in European-ancestry populations. Genetic predisposition to prostate cancer can be determined by GWAS of single-nucleotide polymorphisms (SNPs). Loci that are identified by GWAS can be used to calculate the risk of disease in individuals, and to highlight genomic regions for further investigation in mechanistic and therapeutic studies. GWAS have been primarily conducted in populations of European ancestry, and have identified variant loci that are also associated with risk in other populations. The latest meta-analysis has pooled and reanalysed SNP data from GWAS originally conducted in populations of single ancestry. Between them, these studies comprise a total of 43,303 men with prostate cancer and 43,737 controls

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Genetic risk analysis goes global

of European, African, Japanese and Latino ancestries. An initial analysis, dividing the data according to ancestry, identified 15 new risk loci in the European-ancestry group, which consisted of 34,379 cases and 33,164 controls. No new loci were identified in any of the other single-ancestry groups, all of which included considerably fewer subjects. A combined, multi-ancestry analysis identified a further seven risk

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variants, and one more came from a secondary analysis of the Europeanancestry data looking at disease diagnosis at ≤55 years of age. For 22 of the 23 loci, the associations with aggressive and with nonaggressive prostate cancer were not significantly different. The 23 newly discovered variants are estimated to account for 3.1% of the familial risk of prostate cancer in populations of European ancestry. The 10% of men with the highest risk based on the 100 known SNP variants have a 2.9-fold increase in the relative risk of prostate cancer, and the top 1% have a 5.7-fold increased risk, compared with the population average. Family history and genetic risk could help to define a group of men who would benefit from PSA screening. Robert Phillips Original article Al Olama, A. A. et al. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat. Genet. doi:10.1038/ng.3094

VOLUME 11  |  DECEMBER 2014 © 2014 Macmillan Publishers Limited. All rights reserved

Prostate cancer: genetic risk analysis goes global.

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