More evidence for BRCA2 prostate cancer link

Results from an Icelandic study, published in the Journal of the National Cancer Institute, provide further evidence for the link between BRCA2 gene mutations and prostate cancer. Researchers from the Icelandic Cancer Registry in Reykjavik showed that one particular BRCA2 mutation, 999del5, was present in 1 in 20 of the prostate cancer patients studied and was linked to more aggressive forms of the disease.

While previous research at the Memorial Sloan-Kettering Cancer Centre in New York has shown that men in BRCA2 families are 3-5 times more likely to develop prostate cancer, this is the first time that researchers have taken a more in-depth look at the disease progression in such patients.

According to statistics published by Cancer Research UK, prostate cancer is the most common cancer in men in the UK, affecting 1 in 14, and accounts for nearly a quarter of male cancers. However, deaths from prostate cancer are relatively low since there a two 'grades' of prostate cancer: high-grade cancers may be lethal and will require active treatment through surgery and/or radiotherapy. However many cancers are 'low-grade' and, if small, may never cause any problems within a man's lifetime.

'The big challenge today is how to distinguish between a lethal cancer and a harmless one', said team leader Dr Laufey Tryggvadottir, speaking to New Scientist.

According to the researchers, the BRCA2 999del5 mutation is only carried by around 1 in 200 Icelandic men, with a similar incidence rate across Europe. So to obtain a sample of men liable to have prostate cancer associated with this mutation, Tryggvadottir and colleagues used the Icelandic Cancer Registry to pool prostate cancer patients with female relatives affected by breast cancer, giving a total of 596 men.

DNA analyses of stored tumour samples from these patients revealed that 30 men (5.7 per cent) carried the specific BRCA2 mutation. Furthermore, many of these men had unusually advanced disease at diagnosis and poor survival, dying an average of 10 years earlier than patients who didn't carry the mutation.

Given the probable rarity of the 999del5 mutation, the next stage will be 'to study whether these results can be confirmed for carriers of mutations at other locations within the BRCA2 gene', write the researchers. 'This finding suggests the need for prostate cancer surveillance of carriers of BRCA2 mutations', they conclude.

'In the short run, few men newly diagnosed with prostate cancer will gain much assurance from learning that they do not carry BRCA2 mutations', commented Sholom Wacholder of the National Cancer Institute in Bethesda, in an accompanying editorial. 'In the longer run, studies of the joint effects of treatment and genetic factors on prognosis and survival may allow for more tailored treatment decisions', he concludes.