A new gene connected to hereditary breast cancer susceptibility has been identified in what researchers are calling a landmark study.
The discovery marks the first time in years that a new susceptibility gene has been pinpointed, allowing scientists to get one step closer to a full understanding of hereditary breast cancer.
“We know that genetics play an important role in the likelihood of developing breast cancer, with hereditary breast cancer accounting for roughly ten per cent of all cases,” Dr. Mohammad Reza Akbari, associate professor at the University of Toronto and the principal investigator of the study, said in a press release.
Around one in eight women in Canada will develop breast cancer in their lifetime, with the disease accounting for the highest amount of cancer-related deaths in women globally.
This new information, published Monday in the American Journal of Human Genetics, could allow for more frequent and targeted screening to catch breast cancer earlier, as well as opening up more therapies or treatments that focus on genes.
The gene is called ATRIP, and is linked to DNA stress replication. It appears to be less common than other gene mutations linked to hereditary breast cancer, but when a person has mutations in ATRIP, they are significantly more likely to develop breast cancer, researchers found.
The discovery could explain why scientists frequently encounter patients where breast cancer runs in the family, but none of the family members have well-known gene mutations connected to breast cancer, such as BRCA 1 and BRCA 2.
“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,” Akbari said. “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.”
It was the genes of a group of such families that put them on the path towards identifying ATRIP as a gene of concern.
Akbari, who is also a scientist with the Women’s College Hospital, worked with Dr. Cezary Cybulski at Pomeranian Medical University in Poland and Dr. Jean-Yves Masson from Laval University in Quebec to examine the genetic sequencing of 510 women with hereditary breast cancer in Poland.
This group was matched with 308 control subjects to isolate which genes were different.
There were two women out of the 510 who had the rare mutation in ATRIP. From this small starting point, researchers were able to scan through data on 16,000 further Polish patients with breast cancer, finding the gene variation in 42.
To further confirm it, researchers then looked at data in the U.K. Biobank, a database containing health information on 450,000 individuals.
What they found was that certain mutations in ATRIP were significantly predictive of breast cancer development, and that it wasn’t merely affecting women of Polish descent either.
ATRIP is critical to the process of specialized proteins binding to single-stranded DNA where DNA replication has stalled — when this gene is properly activated, it helps elicit a damage response if there is stress in the replication process of the DNA. Essentially, this gene needs to be functioning correctly to signal to the body after DNA damage, and for proteins to bind correctly.
All cancers are caused by changes in DNA that lead to cells dividing uncontrollably and spreading into other tissues of the body, forming what we know as tumours.
With the isolation of a new gene as one of the problem spots to look out for, researchers believe it will lead to better treatment for those who have this gene and do develop breast cancer.
“While further research is needed, we already know that specific forms of chemotherapy are particularly effective against the breast tumours with homologous recombination deficiency (HRD) observed in patients with a mutated ATRIP gene,” Akbari said. “As a result, those with the ATRIP mutation will now be able to receive more tailored and precise care from their clinical teams – improving their outcomes and chance of survival.”
Currently, Akbari said the team is scanning more families in its data bank with hereditary breast cancer in order to find more matches for ATRIP to better understand its impact on the development of the cancer.
“We know that identifying this genetic mutation will have a meaningful impact on all those affected by familial breast cancer,” he said.
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