Research has already established that men who inherit a faulty BRCA2 gene have a higher risk of developing prostate cancer, but this, the largest study of its kind, is the first to show that the faulty gene also means carriers are more likely to experience more rapid spread of the disease and poorer survival.
The study, reported this week in the Journal of Clinical Oncology, poses a potential challenge to health systems like the UK's NHS where carriers of the faulty gene are offered the same prostate cancer treatment options as non-carriers.
Senior author Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research (ICR) in the UK, says in a statement that the study clearly shows prostate cancers linked to inheritance of the faulty BRCA2 cancer gene are more deadly than other types.
"It must make sense to start offering affected men immediate surgery or radiotherapy, even for early-stage cases that would otherwise be classified as low-risk," says Eeles, who is also Honorary Consultant in Clinical Oncology at The Royal Marsden in London.
However, she also cautions that:
"We won't be able to tell for certain that earlier treatment can benefit men with inherited cancer genes until we've tested it in a clinical trial, but the hope is that our study will ultimately save lives by directing treatment at those who most need it."
BRCA1 and BRCA2 and Prostate CancerNormal BRCA1 and BRCA2 genes help to suppress tumors and protect DNA. Mutations of these genes (spelling mistakes in their DNA code) hamper them carrying out these potentially life-saving functions.
Mutations in BRCA1 and BRCA2 genes were originally spotted in patients with breast cancer. We now know that these faulty genes not only raise the risk of developing breast cancer, but also of ovarian and prostate cancers.
It is not easy to tell at the diagnosis stage whether a man with prostate cancer has the more aggressive type, so while treatment options in the early stage include surgery and radiotherapy, the tendency is to place many patients under active surveillance to see how the disease develops.
1.2% of men with prostate cancer carry the BRCA2 mutation and 0.44% carry the BRCA1 mutation. Carrying the BRCA2 mutation gives a man an 8.6 times higher risk of developing prostate cancer compared to a non-carrier. If a man carries the BRCA1 mutation, he has a 3.4-fold higher risk.
It is not routine in the UK for all men diagnosed with prostate cancer to be offered a test for these faulty genes. Currently in the UK the test is only likely to be offered to men in families with a significant history of breast or ovarian cancer as well as prostate cancer. However, it is expected that as the test becomes cheaper, it will be offered more routinely.
The researchers would like to see the BRCA2 test offered to all men under the age of 65 who develop prostate cancer. A previous study found that 1 in 100 of such patients carries the faulty gene.
In the UK, about 40,800 men are diagnosed with prostate cancer, which claims one life every hour.
Prostate Cancer Patients with BRCA2 Significantly Less Likely to SurviveFor their study, Eeles and colleagues examined the medical records of over 2,000 prostate cancer patients.
61 of the patients carried mutations in BRCA2, 18 had mutations in BRCA1, and 1,940 had neither BRCA1 nor BRCA2 mutations.
They found that compared to non-carriers, patients carrying the faulty genes were more likely to be diagnosed with advanced prostate cancers (37% versus 28%), or with cancer that had already spread (18% versus 9%).
Also, for those patients whose diagnosis showed the cancer had not yet spread, during the five years after diagnosis, it started to spread in 23% of the mutation carriers compared with only 7% of the non-carriers.
Carriers of faulty BRCA2 genes were also significantly less likely to survive. While non-carriers lived an average of 12.9 years after diagnosis, BRCA2 carriers only survived an average of 6.5 years.
The analysis for BRCA1 carriers showed while those patients had a shorter survival average (living 10.5 years after diagnosis) than non-carriers, this was not statistically significant, say the authors.
The study concludes that:
"BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients."
Alan Ashworth, Chief Executive of The ICR, says:
"Our knowledge of cancer genetics is now increasingly shaping the way we treat the disease, by allowing us to offer more intensive treatment, or even different drugs altogether, for people who have inherited cancer genes."
Julie Sharp, Senior Science Information Manager at Cancer Research UK, adds:
"This study shows that doctors need to consider treating men with prostate cancer and a faulty BRCA2 gene much sooner than they currently do, rather than waiting to see how the disease develops."
Funds from the Ronald and Rita McAulay Foundation and Cancer Research UK helped finance the research.
In a huge breakthrough study reported recently in 13 papers in five journals, researchers from the Collaborative Oncological Gene-Environment Study describe more than 80 genome regions that can raise a person's risk of developing prostate, breast and ovarian cancers.
Written by Catharine Paddock PhD