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Researchers crack how BRCA1 gene raises cancer risk

09 October 2017

By Dr Loredana Guglielmi

Appeared in BioNews 921

A major breakthrough in understanding how mutations in the BRCA1 gene raise cancer risk has been made by researchers in the USA.

The BRCA1 gene was known to have a role in repairing DNA damage, which can be caused by exposure to radiation, chemicals and other environmental stressors. Now researchers have shown how it interacts with another gene to trigger DNA repair.

'There have been about 14,000 papers written about BRCA1, and you would think we already know everything about the gene, but we don't,' said Professor Patrick Sung at the Yale Cancer Centre in New Haven, Connecticut, and study leader. 'Defining the mechanism of the BRCA-dependent DNA repair pathway will help scientists design drugs to kill cancer cells more efficiently.'

If a woman has a BRCA1 mutation, by the time she is 70 years old her chance of developing breast cancer is 80 percent, compared with 12 percent if she does not. There is also a higher risk of developing ovarian, prostate and pancreatic cancers.

Despite its discovery almost 20 years ago, the BRCA1 DNA repair mechanism remained unexplained.

'The only way to find out is to purify the proteins, study its properties … and reconstitute the DNA-repair reaction,' said Professor Sung to HealthDay News.

The team showed that BRCA1 interacts with another gene called BARD1 to trigger a cascade of genetic events to repair DNA breaks. The research, published in Nature, describes how mutations occurring in the complex BRCA1-BARD1 and not just the BRCA1 gene affect the DNA repair function, and so raise cancer risk.

The researchers say their findings could be used to determine how harmful a patient's BRCA1 mutation is, which could assist in planning treatment.

'I should be able to tell you what [the mutation] means,' Professor Sung said to HealthDay News. 'We should be able to tell whether it affects the DNA-repair process or not.'

Researchers first believed that BRCA1 and BRCA2 mutations could account for up to eight percent of breast or ovarian cancers. However, this is likely to be higher as in many cancers there is no evidence of mutation, but expression of BRCA genes is still silenced.

'Understanding this mechanism will provide the predictive power for doctors trying to establish a patient's personal risk of developing cancer,' Professor Sung said.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

13 November 2017 - by Dr Loredana Guglielmi 
Researchers have introduced new criteria to screen for BRCA gene mutations that could prevent more than 10,000 cases of cancer and save more than 2000 lives in the next decade...
06 November 2017 - by Isobel Steer 
Machine learning has been used to develop a promising screening test for ovarian cancer, a team of US-based researchers has said...
30 October 2017 - by Annabel Slater 
Two studies have discovered 72 new genetic variants associated with the risk of developing breast cancer...

26 June 2017 - by Lea Goetz 
A study of almost 10,000 women carrying BRCA mutations has revealed the best estimate yet of their risk in developing breast and ovarian cancer...
12 June 2017 - by Dr Loredana Guglielmi 
A drug treatment for ovarian cancer has shown success against inherited breast cancer...
20 March 2017 - by Dr Molly Godfrey 
A genetic study of breast cancer patients suggests that existing drugs for treating rare breast and ovarian cancers may help more patients than previously thought...
25 April 2016 - by Dr Katie Howe 
Women with a mutation in the breast-cancer susceptibility gene BRCA1 may have reduced numbers of eggs left in their ovaries, according to a study led by Australian scientists...

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