Women’s College Hospital Researcher Discovers New Hereditary Breast Cancer Gene

March 27, 2023

Groundbreaking research has identified a genetic mutation strongly linked to breast cancer

Toronto, ON— March 27, 2023 —A landmark study published today in The American Journal of Human Genetics successfully identifies a new breast cancer susceptibility gene called ATRIP. Linked to DNA stress replication, ATRIP mutations appear to be less common than other genetic mutations; however, those with ATRIP mutations are at a significant risk of developing breast cancer. This is the first time in years that a new susceptibility gene has been discovered to help physicians and scientists better understand the origins of hereditary breast cancer.

Breast cancer is the leading cause of cancer-related death in women globally. In Canada, one in eight women will develop breast cancer during their lifetime. “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,” said Dr. Mohammad Reza Akbari, Women’s College Hospital scientist, associate professor at the University of Toronto and the principal investigator of the study.

Identifying individuals with cancer susceptibility genes has important implications for their care. It can lead to more frequent and intensive cancer screening, earlier diagnosis and more targeted therapies or treatments. Knowledge is power. When people are aware of their increased risk of breast and other cancers they can be more proactive and vigilant. Moreover, there are many patients with high rates of breast cancer within their family who do not match with the known gene mutations, like BRCA 1 and BRCA 2. New gene discoveries like this are essential to our understanding of this disease.

“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,” Dr. Akbari shared. “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. 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.”

Dr. Mohammad Reza Akbari collaborated with Dr. Cezary Cybulski at Pomeranian Medical University in Poland and Dr. Jean-Yves Masson at Laval University in Quebec to discover ATRIP as a breast cancer susceptibility gene. To make this discovery, the team initially utilized genetic sequencing on the DNA of a small group of women with familial breast cancer in Poland. This group was selected as it is less genetically diverse than a large mixed population, making it easier to identify genetic variations. 

After identifying ATRIP, the research team then leveraged a larger DNA data set of Polish women with breast cancer and healthy controls to validate the findings. The findings were further investigated using the DNA sequencing data of those with breast cancer registered in the UK-biobank population – confirming ATRIP as a breast cancer susceptibility gene, applicable to women outside of Polish descent. 

“We know that identifying this genetic mutation will have a meaningful impact on all those affected by familial breast cancer,” Akbari stated. “While we are incredibly proud of the work accomplished to date, we still have more to do. Right now, we are screening families in our data bank that have familial breast cancer to see if they match for ATRIP. Going forward our team will continue to investigate further, leveraging DNA data sets across the globe to better understand ATRIP and its impact.”

Reference

The study, “Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK biobank” was published in The American Journal of Human Genetics.

Author Block: Cezary Cybulski, Neda Zamani, Wojciech Kluźniak, Larissa Milano, Dominika Wokołorczyk, Klaudia Stempa, Helena Rudnicka, Shiyu Zhang, Maryam Zadeh, Tomasz Huzarski, Anna Jakubowska, Tadeusz Dębniak, Marcin Lener, Marek Szwiec, Paweł Domagała, Amir Abbas Samani, Steven Narod, Jacek Gronwald, Jean-Yves Masson, Jan Lubiński, Mohammad R. Akbari

About Women’s College Hospital

For more than 100 years Women’s College Hospital (WCH) has been developing revolutionary advances in healthcare.  Today, WCH is a world leader in health equity and Canada’s leading academic ambulatory hospital. It focuses on delivering innovative solutions that address Canada’s most pressing issues related to population health, patient experience and system costs. A multidisciplinary research institute, the Women’s College Research Institute (WCRI), is one of only a few hospital-based research institutes worldwide to focus on health equity. WCRI leads innovative, high-impact health research that changes practice, changes policy, and changes lives.

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