Development of screening algorithm for high breast and ovarian cancer risk by analysis of spectrum of predisposing mutations and their phenotypic manifestations

Aim of the study is to develop screening algorithm for high familial 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 TP53, PTEN, PALB2, CHEK2, ATM. From 2004-2020 5000 unselected breast cancers, including 200 BRCA1 positive cases have been recruited to the 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 a number of selected cases. Genotype-phenotype correlations, including analysis of most accurate selection criteria and clinical risk modifiers of BRCA1/2 will be studied. The development of high breast and ovarian cancer risk screening algorithm will be initiated by analysis of obtained clinical and molecular information.