27 June 2008
A paper in the British Journal of Cancer presents evidence that male carriers of mutations in the BRCA1 or BRCA2 genes (associated with hereditary breast-ovarian cancer syndrome) are not only at five-fold increased risk of prostate cancer compared with the general male population, but also show much more rapid disease progression [Narod SA et al. (2008) Br J Cancer. Jun 24. Epub ahead of print]. This work replicates earlier findings by Icelandic researchers who found a significantly reduced survival for a smaller group of male BRCA2 mutation carriers with prostate cancer [Tryggvadottir L et al. (2007) J Natl Cancer Inst. 99(12):929-35.]
The researchers identified prostate cancer patients from a panel of almost 2700 families with a BRCA1 or a BRCA2 mutation. They compared the median survival times after diagnosis of the 119 men who were “known or probable carriers of a BRCA1 mutation” with 183 men who were ”known or probable carriers of a BRCA2 mutation”. The two groups showed a similar age at diagnosis but median survival time was 8 years for BRCA1 carriers and 4 years for BRCA2 carriers. This compares with an average survival of twelve years from diagnosis for prostate cancer patients in general. Repeat analysis including only the confirmed mutation carriers found a median survival time of 15 years for BRCA1 carriers (37 in total) and 5 years for BRCA2 carriers (67 in total).
Referring to men with BRCA2 mutations, Dr Lesley Walker, of the charity Cancer Research UK, commented: "It is important that more research is done in this area to ensure that this group is targeted effectively so cancer is picked up at an early stage and, more importantly, that they are given the most appropriate treatment” (see BBC news). Confirmed male mutation carriers should receive increased levels of PSA screening for prostate cancer, from an earlier age than the general population.
Comment: Improved understanding of genetic predisposition to cancers can refine screening strategies and improve survival for high risk groups without imposing excessive screening on those at lower risk. This is an important example of public health genomics in practice. Such information may also be important for clinical management of cancer patients.
The researchers acknowledge limitations to this study, notably the relatively small sample size and the lack of a control group of non-mutation carrier prostate cancer patients. They do, however, note that the ten-year death rate of prostate cancer patients has been reported as 27-32% compared with 75% for the BRCA2 carriers in their own study. It is proposed that a larger study should investigate the prognosis of BRCA2 mutation carrier prostate cancer patients and their response to alternative treatments, in particular whether they might benefit from specially targeted chemotherapeutics.