Medical Research: What are the main findings of the study?
Dr Batra: Prostate cancer is a disease with upto 40% genetic component. Previous Genome-wide association studies have identified 77 risk loci associated with prostate cancer. This study is further extension of previous GWASs and also involved meta-analysis of multi-ethnic populations. Through this large study involving approximately 90,0000 individuals, 23 new susceptibility loci were identified to be associated with prostate cancer, 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer.
Medical Research: What was most surprising about the results?
Dr Batra: Previous prostate cancer GWAS have been focused on European population, with the majority of risk loci that have been discovered also found to be associated with prostate cancer risk in other populations. Thus in effort to identify additional prostate cancer risk associated loci; the study undertook a meta-analysis of multiethnic ethnic populations and identified additional 7 variants in addition to new 15 variants identified in European population. The meta-analysis has provided additional power to the study leading to this novel outcome. These 23 variants, in combination with known prostate cancer risk variants, explain one third of the familial risk for this disease in European-ancestry populations.
Medical Research: What should clinicians and patients take away from your report?
Dr Batra: The study brings the total number of common genetic variants linked to prostate cancer to 100, and testing for them can identify 1% of men with a risk of the disease almost six times as high as the population average. Although more studies are required to understand the clinical implications of these results as diagnostic and prognostic biomarkers of prostate cancer, what the take home message is that the combination of many small risk factors can combine to form a high risk score. A well designed clinical trial is now required to evaluate if testing for these 100 genetic variants in men can successfully pick up the disease early, and help direct targeted interventions for patients.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr Batra: It is estimated that around 1000 small effect risk loci are associated with prostate cancer. Thus future research should be focussed on identifying these loci, which should be able to explain at least a part of the missing heritability (2/3rd) factors behind the disease. In addition, we have still not found low risk genetic variants which could distinguish aggressive and non-aggressive form of the disease and future genetic studies should be targeted towards that. We also need to understand the functional role of these variants i.e. how these variants can affect the pathology of prostate cancer including its initiation and progression. So we have a long way to go.
A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer
Nature GeneticsYear published:(2014)DOI: doi:10.1038/ng.3094Received 26 March 2014 Accepted19 August 2014 Published online14 September 2014
Christopher A Haiman et al. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nature Genetics, 2014; DOI: 10.1038/ng.3094