BRCA-CARRIER Cancer risk assessment and radiosensitivity on BRCA pathogenic mutation carriers

Overview

Project Summary

Mutations in the BRCA genes are associated with hereditary breast and ovarian cancer (HBOC) syndrome. Portugal ranks at the top of the incidence rates of the BRCA2 mutation (mBRCA2) in Europe, which is justified by the existence of a Portuguese founder mutation associated with the BRCA2 gene, c.156_157insAlu (BRCA2_PT), present in more than half of all mBRCA2. The BRCA2 gene plays a crucial role in the repair of DNA double-strand breaks (DSB), one of the worst injuries associated with ionizing radiation (IR), so mutations could disrupt these mechanisms and lead to carcinogenesis, conferring augmented radiosensitivity to mBRCA2 carriers.

The clinical follow-up of women belonging to HBOC families includes periodic mammography, a low-dose IR examination (LDIR) to screen for breast cancer. In addition, these individuals are also exposed during their lifetime to other imaging exams with LDIR (e.g. X-ray or computed tomography). Several retrospective epidemiological and experimental studies have shown that exposure to LDIR increases cancer-risk in individuals with HBOC. However, these studies are very inconsistent and present several limitations. Data on the effects of LDIR in healthy carriers of mBRCA2 are very scarce, and there is none focusing on BRCA2_PT.

So, the main objective of the BRCA-CARRIER project is to assess whether an individual carrying BRCA2_PT can perform imaging diagnostic exams using LDIR without an increased disease-risk. 

The project's research plan encompasses the recruitment of non-carriers and BRCA2_PT carriers for the collection of blood and tissues (skin and breast) samples, which will be used for the development of representative ex vivo models of BRCA2_PT. The models obtained will be irradiated in order to characterize the radiosensitivity and biological effects induced by exposure to LDIR.

Main Goals

BRCA-CARRIER project aims to contribute to acquire new knowledge on the risk of using IR diagnostic imaging techniques in individuals with this causal variant in the BRCA2 gene from basic research studies, and to improve health literacy on HBOC. At the end, we intend to provide tools to empower citizens and health professionals, to be informed and to inform, to be educated and to educate, to learn and to teach, to prevent the harmful IR effects.

Project Details