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Genetic test identifies very highest risk men for prostate cancer

18 June 2018
Appeared in BioNews 954

Sixty-three novel gene variants linked to prostate cancer have been discovered. 

The 63 new variants discovered add to the 85 genetic markers already associated with this form of cancer. With the findings, the researchers devised a genetic test that could identify the top one percent of men at risk of developing the disease. One of the mutations discovered was linked to early-onset prostate cancer. 

'The reason we are particularly excited by the test is that this can be offered in general practice as a spit test to really try and identify who is most at risk of prostate cancer so we can offer them targeted screening,' said Professor Rosalind Eeles of London's Institute of Cancer Research (ICR), an author of the study, published in Nature Genetics.

Professor Eeles and her colleagues used a genome-wide association study to compare new and existing DNA data of 80,000 patients with prostate cancer with 61,000 healthy controls. 

Many of the mutations identified may be involved in immune system communication, with others linked to DNA-repair processes. 

A trial of the genetic test for prostate cancer is now being rolled out among a number of GP practices in London. It requires participants to give a saliva sample, which can then be analysed for genetic predisposition to the disease. The results could then be used to identify the men that might benefit from increased monitoring, MRI scans and biopsies. 

'This new research could help men to understand their individual genetic risk of prostate cancer, which could prompt them to speak to their GP about the disease,' said Dr Iain Frame, director of research at Prostate Cancer UK.

However, the mutations the test is screening for only account for about 28 percent of a man's risk of developing prostate cancer. The researchers suspect that the remaining cases are caused either by extremely rare mutations or an accumulation of several smaller mutations, which have no significant impact taken alone but together might trigger prostate cancer development.

In a second study, led by researchers at the University of Michigan and published in the journal Cell, researchers have identified a novel subtype of prostate cancer likely to be responsive to immunotherapy. 

Men with a mutation in both copies of the CDK12 gene appear to benefit from immunotherapy. The researchers found that about seven percent of late-stage prostate cancer patients and one percent of patients in earlier stages of the disease would be likely to respond to the treatment. 

'Immunotherapy works for a relatively small group of men with advanced prostate cancer – but when it works, it really works,' said study author Professor Johann de Bono, Regius Professor of cancer research at the ICR. 'In the future, a genetic test could help pick out men with this particular set of genetic changes, so that they can be considered for immunotherapy.'

SOURCES & REFERENCES
Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
Nature Genetics |  11 June 2018
Inactivation of CDK12 Delineates a Distinct Immunogenic Class of Advanced Prostate Cancer
Cell |  14 June 2018
New Prostate Cancer Subtype Identified, Responsive to Immunotherapy
Genetic Engineering and Biotechnology News |  14 June 2018
Trials begin of a saliva test for prostate cancer
The Guardian |  11 June 2018
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