Development of genetic testing strategies for hereditary breast and ovarian cancer risk prediction by analysis of spectrum of predisposing mutations and their phenotypic manifestations

Aim of the study is to develop genetic testing strategies for hereditary breast and ovarian cancer risk detection. According to population wide study performed by Institute of Oncology, Riga Stradins Universty, BRCA1 pathogenic founder variants (c.4035delA, c.5266dupC) contribute to 3.77% of all consecutive primary breast cancers and 9.9% of all consecutive primary ovarian cancers in Latvia. However, there are no systematic studies carried out about the frequency, spectrum and clinical features of pathogenic BRCA1/2 non-founder variants as well other predisposing genes, including PALB2, CHEK2, ATM. From 2004-2020 6000 unselected breast and ovarian cancers, including 350 BRCA1/2 positive cases have been recruited to the unique registry of Institute of Oncology, Riga Stradins University. For all cases clinical data and DNA samples are available. Testing of breast and ovarian cancer predisposing gene mutations will be performed in 1000 selected cases. Genotype-phenotype correlations, including analysis of most accurate selection criteria and clinical risk modifiers of BRCA1/2 will be studied. Hereditary breast and ovarian cancer risk genetic testing strategies will be developed by analysis of obtained clinical and molecular information.