Breast cancer

BRCA variant study sorts out the wheat from the chaff

Tuesday, 25 Jun 2019


A/Prof Amanda Spurdle

An international study led by Queensland researchers has examined hundreds of BRCA1 and BRCA2 pathogenic and benign variants to isolate those that have most clinical relevance.

The study, led by scientists at the QIMR Berghofer Medical Research Institute, Brisbane,  collated research and clinical data in a multifactorial likelihood analysis of 1395 BRCA1/2 predominantly intronic and missense variants.

It discovered that 94 genetic variants, about which little has been known until now, are associated with an increased risk of developing breast, ovarian, prostate and pancreatic cancers.

The study also identified 447 other genetic variants in the BRCA1 and BRCA2 genes did not cause cancer.

The genetic knowledge obtained by the ENIGMA international consortium will help identify people at risk and help clinicians and genetic counsellors decide on the best management for people who carry variants in the BRCA1 or BRCA2 cancer genes.

Published in Human Mutation, the review involved more than 200 scientists and doctors from 114 institutions in 15 countries, working on some of the 20,000 variants in the BRCA1 and BRCA2 cancer genes.

Senior Author and head of QIMR Berghofer’s Molecular Cancer Epidemiology Group, Associate Professor Amanda Spurdle, said it was the single largest study of its type to date.

“We were able to weed out 447 variants as harmless, while showing 94 variants did increase a person’s risk of developing breast, ovarian, prostate and pancreatic cancers”, she said.

“It’s like separating the wheat from the chaff.

“These findings will help doctors give advice on the frequency of early screening such as breast scans; preventative measures such as risk-reducing surgery or medication; and even personalised treatment with specific drugs (PARP-inhibitors) for people with those cancers.

The new genetic variant information can also used to decide whether to test close relatives for cancer risks, she added.

“If we can narrow down which variants pose a danger, we can reduce concern for clinicians and patients, and avoid unnecessary testing that unfortunately sometimes occurs for individuals with a variant of uncertain significance.”

“Importantly, it has also provided a basis for us to further develop our methods for classifying genetic variants in future.”

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