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BRCA mutations linked to prostate and uterine cancers

11 July 2016

By Antony Blackburn-Starza

Appeared in BioNews 859

Genetic mutations on several genes including BRCA2 have been associated with prostate cancer; while in a separate study, a BRCA1 mutation has been linked to a particular form of uterine cancer

The first study, published in the New England Journal of Medicine, found that 12 percent of men with advanced prostate cancer had inherited mutations in genes involved in the repair of damaged DNA.

Professor Johann de Bono of the Institute of Cancer Research in London and the Royal Marsden NHS Foundation Trust, who led the study, said: 'Our study has shown that a significant proportion of men with advanced prostate cancer are born with DNA repair mutations – and this could have important implications for patients.

'Genetic testing for these mutations could identify men with advanced prostate cancer who may benefit from precision treatment. We could offer these men drugs such as PARP inhibitors, which are effective in patients with certain DNA repair mutations and are showing important anti-tumour activity in ongoing clinical trials.'

The researchers examined 20 genes known to play a role in the repair of damaged DNA in 692 cancer patients from the US and the UK. Of those, mutations in the BRCA2 gene accounted for five percent of cases. Mutations in the BRCA1 gene were also identified.

'Where we find BRCA2 mutations, we could also offer genetic testing and counselling to relatives of the patient to consider how we can reduce their cancer risk. We also need to establish the impact of having DNA repair defects on survival in men with prostate cancer, and whether we can predict who will develop severe disease, so we can design new treatment strategies to cure this disease,' said Professor de Bono.

Dr Imran Ahmad of Cancer Research UK, which part-funded the study, said that the number of mutations associated with prostate cancer risk in the study was surprising. 'This new research shows that there are more inherited mutations affecting the DNA-repair machinery in some men with advanced prostate cancer than was previously thought,' he said.

Elsewhere, scientists at Duke Cancer Institute in the US identified that women with the BRCA1 gene mutation, which increases the risk of breast and ovarian cancer, also have a higher risk of uterine cancer.

'This is the study that has been needed,' said lead author Dr Noah Kauff. 'Our study presents the strongest evidence to date that women with this genetic mutation should at least discuss with their doctors the option of having a hysterectomy along with removal of their ovaries and fallopian tubes.'

The researchers in this study, published in JAMA Oncology, examined data collected over an average of five years from more than 1000 women with BRCA1 or BRCA2 mutations and who had their ovaries and fallopian tubes removed. Among the BRCA-positive women, eight reported uterine cancers – a rate similar to the national norm.

However, five of the eight women reported a particularly serious sub-type of uterine cancer called serous endometrial cancer, and all but one of those occurred in patients with a BRCA1 mutation.

'We were surprised when we saw the data,' Dr Kauff said. 'This is an event that should not occur in the over 600 women with BRCA1 mutations in our study. Even if we followed these women for 25 years, you would only expect to see no more than one serous cancer.'

He said: 'Our findings suggest that it may be important for women with BRCA1 mutations to consider removing their uterus at the time they are considering removing their ovaries and fallopian tubes, unless they are hoping to still have children using assisted reproductive methods or have other medical reasons.'

However, Dr Kauff added that the findings may be less clear for women who have already had their ovaries and fallopian tubes removed and more research would need to be undertaken to determine if the cost and risks of a second operation could be justified.  

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