Geneticists from the Research Institute of the Hospital de Sant Pau – IIB Sant Pau and the IFOM – Instituto FIRC di Oncologia Molecolare of Milan (Italy), led by doctors Jordi Surrallés and Paolo Peterlongo respectively, have discovered that certain rare mutations in the FANCM gene constitute a predisposition factor for developing ER and triple-negative breast cancer, considered to be the most aggressive and with the worst prognosis among the different types of breast cancer.
The study, carried out by researchers from Sant Pau – who are linked to the CIBER of rare diseases (CIBERER, Unit U745) and the UAB-IR Sant Pau Joint Unit of Genomic Medicine – and those of the IFOM – Instituto FIRC di Oncologia Molecolare de Milan, was carried out by assessing the association of three recurrent variants of the FANCM gene with the risk of developing breast cancer at 67. 112 cases, 53,766 controls and 26,662 carriers of pathogenic variants BRCA1 or BRCA2. The research involved more than 200 laboratories and hospitals worldwide within the framework of the OncoArray Consortium, a multinational collaboration established to discover variants that predispose to different human cancers such as breast, colon, lung, ovarian, endometrial and prostate.
Dr. Massimo Bogliolo, member of the team and first signatory of the article explains that “genetic data indicate that one of the genetic variants in FANCM analyzed is associated with a 3.8 times higher risk of developing triple negative breast cancer and 2.44 times higher risk of developing ER-negative breast cancer”.
The researchers also functionally studied the mutations in cellular models to analyze their role in the response to olaparib, a drug for the treatment of ovarian cancer, or breast cancer for patients with BRCA1 or BRCA2 mutations who have advanced disease that is resistant to other treatments. The functional data showed that the genetic variants effectively altered the function of the FANCM gene producing greater sensitivity to the anti-tumour effect of olaparib, suggesting that this drug could be a possible therapeutic alternative to treat patients with breast tumours associated with pathogenic variants of FANCM.
The study has been published in Nature Partner Journals Breast Cancer (NPJ Breast Cancer)
