Novel breast cancer susceptibility gene variant identified

A rare gene mutation that may increase risk of breast cancer, has been identified in women of Polish descent.

The ATRIP gene was already known to play a role in DNA replication, but had not previously been linked to breast cancer. Researchers studying the genomes of Polish women with breast cancer identified a variant of the gene which potentially doubles carriers' overall lifetime risk of breast cancer to over 20 percent. Further research by the team from the Pomeranian Medical University, Szczecin, Poland and collaborators in Canada suggested this variant could be carried by over 25,000 Polish women.

'Our lab regularly receives referrals from all over the world, where multiple members of the same family are diagnosed with breast cancer, indicating a genetic predisposition. Despite this, we are unable to match many of them with known breast cancer genes. Now that ATRIP has been identified, more families will be able to get the answers they deserve,' said lead author and principal investigator Dr Mohammed Akbari, from the University of Toronto, Canada.

Hereditary breast cancer accounts for approximately ten percent of all breast cancer cases. Mutations known to increase the risk of breast cancer such those in the BRCA1 and 2 genes can also increase the risk of ovarian and other cancers, including prostate cancer in men (see BioNews 1130). Women with a family history of breast or ovarian cancer may require increased surveillance or prophylactic surgery to reduce their risk if found to carry a genetic variant that increases their susceptibility.

The scientists discovered the ATRIP variant's effect by comparing whole exome data from a small cohort of Polish women: 508 who had familial breast cancer and 308 unaffected controls.  They then validated this finding on a larger cohort of over 25,000 women in Poland, and again with UK Biobank data. This confirmed the higher frequency of this variant in women of Polish descent.

Implementing more frequent cancer screening for individuals with these variants could help to detect breast cancer earlier, which could improve outcomes. Furthermore, this discovery may promote the use of more effective targeted treatments during a cancer diagnosis.

First author Dr Cezary Cybulski, from the Department of Genetics and Pathomorphology at the Pomeranian Medical University said the findings could help to create 'a simple and cheap test to detect the mutation in the ATRIP gene' that would be available to Polish women before the end of 2023. He added: 'Patients who test positive will be advised to undergo preventive screening earlier in their lives, namely breast ultrasonography from the age of 25 and mammography from the age of 35.'