Scientists from Poland and Canada have discovered a new gene whose mutations cause a high risk of breast cancer! The international team of researchers was led by Cezary Cybulski, a geneticist from the Department of Genetics and Pathomorphology at Pomeranian Medical University, and Mohammad Akbari from the University of Toronto.
ATRIP - a new breast cancer gene
Published March 27, 2023 20:28
iStock/Getty Images
The detection of the new gene was made possible by the identification of the ATRIP repeat mutation (c.1152_1155del; p.Gly385Ter) in a genetically homogeneous Polish population. The study included 16,000 breast cancer patients and 9,000 healthy women. The researchers' results suggest that carriers of the "Polish" mutation have an increased risk of developing breast cancer by more than 2 times, at more than 20%. If breast cancer was found among relatives of carriers of this mutation, the risk of the disease is more than 30%. The number of carriers of mutations of the ATRIP gene in Poland is estimated at about 25 thousand.
ATRIP mutations have been found to segregate with cancer in families with strong breast cancer aggregation. In addition, through analysis of the UK biobank (450,000 people), pathogenic ATRIP mutations (more than a dozen different mutations) were found to increase the risk of breast cancer more than 3-fold in the UK. The prevalence of ATRIP mutations in the UK suggests that they are likely to cause breast cancer in many other ethnic groups around the world as well.
According to researchers at PUM in Szczecin, later this year patients will be able to check during diagnostic tests whether they are carriers of the mutated ATRIP gene. In case of a positive result, recommendations will include more frequent examinations and mammograms starting at age 35. Since cancers in women
with the ATRIP mutation have impaired DNA repair by homologous recombination, they are likely to respond well to treatment with chemotherapy (e.g., cisplatin, PARP inhibitors).
The detection of the repetitive (founder) ATRIP mutation in Poland makes possible a simple and inexpensive test for detecting this mutation. This test can be added to the test for detecting about 10% of breast cancer cases in Polish women by testing a panel of a dozen repetitive mutations of the BRCA1, BRCA2, CHEK2, PALB2, NBN, RECQL genes in Poland. The sensitivity of such a test in detecting mutations of the above genes in Poland is more than 80%.
Development of tests based on founder mutations is possible in genetically homogeneous populations like Poland. Founder mutation tests offer an opportunity for low-cost, rapid, high-sensitivity diagnosis of high-risk cancers in Poland. They should be performed in the first line of diagnosing hereditary predisposition to breast cancer, before using complicated and expensive tests based on next-generation sequencing, with incomparably lower throughput.
The findings of the Polish and Canadian scientists were published in the prestigious journalAmerican Journal of Human Geneticsin 2023.
The new gene was discovered based on a National Science Center project carried out at the Department of Genetics and Pathomorphology at the Pomeranian Medical University in Szczecin in collaboration with the Women's College Research Institute at the University of Toronto.
infra
