Predicting prostate cancer

LONDON—A team of researchers from The Institute of Cancer Research (ICR) have posted results from a recent study revealing that screening men with a family history of prostate cancer can identify those at risk of aggressive forms of the cancer subtype. In their work, which was funded largely by Prostate Cancer UK and in part by Cancer Research UK, the scientists announced that such screening proved capable of identifying 13 mutations in known cancer genes that could predict development of the disease.

“Our study shows the potential benefit of putting prostate cancer on a par with cancers such as breast cancer when it comes to genetic testing. Although ours was a small, first-stage study, we proved that testing for known cancer mutations can pick out men who are destined to have a more aggressive form of prostate cancer,” said Prof. Ros Eeles, professor of Oncogenics at the ICR and honorary consultant at The Royal Marsden NHS Foundation Trust.

“We already have the technical capabilities to assess men for multiple mutations at once, so all that remains is for us to do further work to prove that picking up dangerous mutations early can save lives,” Eeles, who is a co-leader of the study, continued. “If so, then in the future, genetic testing may be needed as part of the prostate cancer care pathway.”

The research team analyzed blood samples from 191 men with prostate cancer, and used new second-generation DNA sequencing technologies to determine mutations in 22 different known cancer genes at once.

The ICR scientists also looked at men who presented with three or more cases of prostate cancer in their family, similar to how breast cancer risk is partially determined and tested for based on family history. As a result, they discovered 13 “loss of function” mutations, in which the genes cannot produce properly working proteins, in eight DNA repair genes; the tested genes included BRCA1, BRCA2, ATM, CHEK2, BRIP1, MUTYH, PALB2 and PMS2. Patients with any of the discovered 13 mutations had an increased risk of developing an invasive form of prostate cancer that could spread, and an increased risk of dying from their cancer.

“One of the important messages to come out of our study is that mutations to at least eight genes – and probably many more – greatly increase the risk of aggressive prostate cancer. Any future screening program would need to assess as many of these genes as possible – more than we currently look for in women at risk of breast cancer, for example,” study co-leader Dr. Zsofia Kote-Jarai, senior staff scientist at the ICR, commented in a statement.

According to Cancer Research UK, prostate cancer represents the fourth most common cause of cancer death in the United Kingdom, and the second most common cause of cancer death among men in the country, as of 2011. The disease accounts for approximately 7 percent of all cancer deaths in the United Kingdom, and 13 percent of all male cancer deaths.

“The minefield of prostate cancer diagnosis is one of the biggest hurdles facing treatment of the disease today. Current tests fail to differentiate between aggressive cancers that could go on to kill, and cancers that may never cause any harm. This lack of clarity means that too often men and their doctors are left having to make incredibly difficult decisions on whether to treat the disease or not,” noted Dr. Iain Frame, director of Research at Prostate Cancer UK. “We urgently need to understand more about which men are at risk of developing prostate cancer and in particular aggressive forms of the disease. Genetic testing to predict risk could revolutionize how we treat the 40,000 men diagnosed with the disease every year in the UK. These results are exciting as they add to the growing weight of evidence that men with a family history of prostate cancer who possess certain genes may be at higher risk, providing us with another crucial piece of the jigsaw.”

SOURCE: The Institute of Cancer Research press release