New Genes for Prostate Cancer Risk, Hope for Screening Test

Alexander M. Castellino, PhD

September 16, 2014

A large meta-analysis that included 87,040 individuals has identified 23 new genetic variants for prostate cancer susceptibility, bringing the total number of common genetic variants linked to prostate cancer to 100. Together, these 100 genetic variants may explain 33% of inherited risk for prostate cancer in European men, and there is hope that they may eventually be useful in a screening test.

The new findings come from a huge global research effort led by scientists at the Institute of Cancer Research in London, the University of Cambridge, United Kingdom, and the University of Southern California. The study was published online in Nature Genetics on September 14.

"The research emphasizes the importance of common genetic variation in the etiology of prostate cancer, and the importance of large-scale international genetics consortia," co–principal investigator Christopher Haiman, ScD, professor of preventive medicine at the Keck School of Medicine of the University of Southern California, said in a press release.

Meta-analysis of 87,040 Individuals

For the meta-analysis, data were combined from genome-wide association studies in individuals across several populations, which included European (34,379 case patients and 33,164 control individuals), African (5327 case patients and 5136 control individuals), Japanese (2563 case patients and 4391 control individualss), and Latino (1034 case patients and 1046 control individuals) ancestries.

The part of the meta-analysis that focussed on studies conducted in people with European ancestry identified 15 variants. Although no risk variants were identified in ancestry-specific analyses across the African, Japanese, or Latino ancestries, 7 new variants were identified across the multiethnic ancestries, and 1 was identified from an early-onset analysis in men younger than 55 years.

Of the 23 variants, 12 risk variants may appear to have functional significance and have the potential to be targeted for therapeutic intervention.

Implications for Prostate Cancer

The researchers estimated that together, 100 genetic variants that are now known may explain 33% of inherited risk for prostate cancer in European men. In addition, the 10% of men at highest risk are close to 3 times more likely to develop prostate cancer compared with the average individual; the top 1% are approximately 6 times more likely to develop the disease.

"Using the information, we may more accurately predict the risk for prostate cancer in men compared with the prostate specific antigen (PSA) test that is currently routinely used and is associated with a high level of false positives," Jong Park, PhD, associate member of the Cancer Epidemiology Program at the Moffitt Cancer Center in Tampa, Florida, who is a coauthor of the study, told Medscape Medical News.

The 100 genetic variants correlate with risk for prostate cancer in European men. "Since Caucasians in the United States are generally of European descent, these genetic variants can be used to determine risk for prostate cancer in Caucasian Americans. However, different genetic variants are expected for African Americans and Latinos, and these may not overlap with the genetic variants for European men," Dr. Park told Medscape Medical News.

The numbers of men with African, Latino, and Japanese ancestries in these analyses were low, and so the study was underpowered to tease out genetic variants in men from these ethnicities.

Genetic Testing for Prostate Cancer

There is great hope that the genetic variants for prostate cancer can be used to develop a genetic test to identify individuals at risk for prostate cancer.

"The results of this study could take us a step closer to targeted screening by allowing us to identify those most at risk of the disease, based on the genes they possess," Dr. Matthew Hobbs, deputy director of research at Prostate Cancer UK, said in a press release. The challenge now lies in translating this knowledge into a reliable test that can be used on a large scale to find those men at highest risk, he added.

Professor Rosalind Eeles, PhD, FRCP, FRCR, professor of oncogenetics at the Institute of Cancer Research, London, and co–principal author, said in a news item: "We can now explain a third of the inherited risk of prostate cancer, and will shortly be conducting a clinical trial to find out whether testing for genetic variants in men can successfully pick up the disease early and help direct targeted interventions for patients."

The UK team is now planning a clinical trial called BARCODE, which will screen 5000 men with these genetic markers.

The study was funded by Cancer Research UK, Prostate Cancer UK, the European Union, and the National Institutes of Health in the United States. The authors have disclosed no relevant financial relationships.

Nat Genet. Published online 14 September, 2014. Abstract

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