Alterations in a man's genetic make-up which lead to aggressive prostate cancer

What you need to know

  • Prostate cancer has a significant genetic risk, and DNA repair genes are often affected
  • We funded Professor Eeles to carry out the largest-scale study of faulty DNA repair genes in prostate cancer to date
  • The team found a strong link between aggressive prostate cancer and certain DNA repair genes. They have since created a test to spot these mutations, and help guide treatments.
We found four key genes which are mutated in 1 in 30 men with prostate cancer. Our results open up possibilities for targeted treatments in these individuals.
Professor Rosalind Eeles

Prostate cancer is one of the most heritable cancers, meaning it can be caused by mutations in men’s genes that are passed on from their parents. Professor Eeles had previously analysed a group of genes called DNA repair genes and found that mutations in these can make men at higher risk of developing advanced prostate cancer.

In this project, she carried out a much larger investigation, looking at almost 200 DNA repair genes in many more men, making it the largest study of its kind.

Finding the DNA repair genes responsible

The team compared the DNA repair genes in blood samples from 1000 men with prostate cancer and 1000 men without prostate cancer, looking for genes that are more commonly faulty in men with prostate cancer.

Next, they determined whether these mutations caused more aggressive forms of prostate cancer, which they measured as a Gleason score of 8-10, or cancer that has spread outside the prostate. 

One in eight prostate cancers have faulty DNA repair genes

The team confirmed their suspicions that men with prostate cancer are more likely to have an inherited DNA repair gene mutation, with one in eight men with prostate cancer having a fault in one of the genes the team tested for.

Of these genes, there are four which are mutated most often, and one gene, called BRCA2, was found to be particularly linked to aggressive prostate cancer.

A new diagnostic test and route for precision medicine

Since finding that many men with prostate cancer have more DNA repair gene mutations, the team has created a genetic test to spot these mutations in men.

This test could be used not only to help diagnose men, but also to work out if they would respond well to certain kinds of treatment, like olaparib, which is more effective in men with defects in DNA repair genes.

The team has already begun testing the use of the genetic test as a diagnostic tool, and has received funding from us to try using it as a way to select men for olaparib treatment.

Grant information

Researcher - Professor Rosalind Eeles and Dr Zsofia Kote-Jarai
Institution - Institute of Cancer Research
Grant award - £205,703
Duration - 2014-2017
Reference - PG13-001 Eeles