Penetrance of CHEK2 and BRCA1 Double Heterozygotes in Breast and/or Ovarian Cancer Patients

Abstract

Abstract Germline pathogenic BRCA1 variants confer increased risk of breast and/or ovarian cancer. The penetrance of BRCA1 pathogenic variants is variable due to the effects of other genetic factors. The interaction between CHEK2 and BRCA1 proteins is crucial in homology directed DNA repair pathway. The aim of this study was to assess the effect of three pathogenic/likely pathogenic variants of the CHEK2 gene on BRCA1 pathogenic allelic variant penetrance. The analysis included 380 DNA samples of women with confirmed positive BRCA1 status for one of founder variants c.4035del and c.5266dup. The c.444+1G>A and c.470T>C variants of CHEK2 gene were identified by Sanger’s sequencing, and the del5395 variant was detected by multiplex PCR. The studied CHEK2 variants were found in 13 double heterozygous cases (c.444+1G>A, n = 1; c.470T>C, n = 11, del5395, n = 1). Although the prevalence of CHEK2 variants in the ovarian cancer group was comparatively high (5.41%), the increase of the ovarian cancer risk was not statistically significant (OR = 1.56; 95% CI: 0.32–9.94; p = 0.73). The association of the age at the onset of cancer with the presence of particular CHEK2 variant was not consistent.