Genetic Screening Can Identify Men at Higher Risk of Aggressive Prostate Cancer

Genetic mutations have been identified that facilitate screening of men for prostate cancer, particularly men with a family history of the disease, to identify those who are at higher risk of aggressive forms and in need of lifelong monitoring.

Scientists at The Institute of Cancer Research, (ICR; London, UK) found 13 mutations in known cancer genes that predicted the development of the prostate cancer (PrCa). The findings demonstrate not only that some men have a genetic profile that puts them at higher risk of PrCa, but that particular genetic profiles match to a higher risk of advanced, invasive disease. “The minefield of PrCa 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," said Dr. Iain Frame, Director of Research at Prostate Cancer UK.

In the study, published by Leongamornlert et al. in the British Journal of Cancer, online ahead of print February 20, 2014, the researchers examined men with a history of three or more cases of PrCa in their close family, in order to mirror use of family history as a criterion for current gene testing programs in breast cancer. Blood samples from 191 men with PrCa at several different UK centers were analyzed. New “second generation” DNA sequencing technologies were used to assess mutations in 22 different known cancer genes simultaneously, opening up, for the first time, the prospect of rapid genetic screening for PrCa for a wide range of mutations.

The results showed 13 loss-of-function mutations among 8 DNA-repair genes. The eight genes were BRCA1 and BRCA2 (already routinely tested for in women with a strong family history of breast or ovarian cancer) plus ATM, CHEK2, BRIP1, MUTYH, PALB2, and PMS2. Men with ANY of these 13 mutations were much more likely than those without to develop an advanced, invasive form of cancer, which spread to the lymph nodes or other parts of the body, and to die from the disease.

“Our study shows the potential benefit of putting PrCa 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 PrCa", said study co-leader Prof. Ros Eeles, professor of Oncogenics at the ICR. Fellow study co-leader Dr. Zsofia Kote-Jarai, senior staff scientist at the ICR, added, “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 PrCa. Any future screening program would need to assess as many of these genes as possible.”

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Institute of Cancer Research