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Seven novel prostate susceptibility loci identified

Analysis of a study published in a science journal   |   By Dr Gurdeep Sagoo   |   Published 19 July 2011
Study: Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study
By: Kote-Jarai Z. et al. (134 authors total)
In: Nature Genetics
Link: http://dx.doi.org/10.1038/ng.882
What this study set out to do:

The study authors conducted an extensive investigation to identify novel common prostate cancer susceptibility loci

How they went about it:

In the first two stages of this study, researchers used computer-based methods to combine data from their previously published genome-wide association study (GWAS) with another prostate cancer study (CGEMS) in order to identify single nucleotide polymorphisms (SNPs) for further analysis. Stage 3 of the study involved more than 1,300 SNPs being genotyped in nearly 5,000 prostate cancer patients and 5,000 healthy men from the UK and Australia. identified SNPs were then replicated in a further 26,000 cases and 25,000 men in the fourth stage.

Outcome:

Sixteen SNPs across 10 loci were identified in the third stage of this study. Of these ten loci, seven were novel loci that lie in regions that contain plausible causative genes. The SNP on chromosome 5 (rs2242652) is located within an intron of the TERT gene in a region linked to several other cancers. Interestingly, this SNP also showed an association with serum prostate-specific antigen (PSA) that was consistent with its prostate cancer association.

Conclusion:

The identification of these seven novel loci brings the total number of known prostate cancer susceptibility loci to 40. These 40 loci are thought to account for around 25% of the familial risk. The top 1% of the population at highest risk are estimated to be at more than a four-fold increase in relative risk compared to the average risk in the general population with potential use of this information including targeted screening and prevention programs.

Our view:

A more than two-fold increase in relative risk for the top 10% of the population and a four-fold increase for the top 1% are no doubt large enough to be clinically useful. However, whether those individuals at the highest genetic risk are also at the highest risk of developing the aggressive form of disease needs further research in order to provide evidence for the clinical utility of screening and prevention programs. The PHG Foundation is a partner in a large European consortium, the Collaborative Oncological Gene-environment Study (COGS), a project that is developing the understanding of both genetic and environmental risk factors for breast, ovarian and prostate cancers, for use in individual risk prediction.

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