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PETBioNewsNewsResearchers crack how BRCA1 gene raises cancer risk

BioNews

Researchers crack how BRCA1 gene raises cancer risk

Published 19 October 2017 posted in News and appears in BioNews 921

Author

Dr Loredana Guglielmi

Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the output from a DNA sequencing machine.
CC BY 4.0
Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the sequencing output from an automated DNA sequencing machine.

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

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.

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