<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Germline pathogenic <italic>BRCA1</italic> variants confer increased risk of breast and/or ovarian cancer. The penetrance of <italic>BRCA1</italic> 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 <italic>CHEK2</italic> gene on <italic>BRCA1</italic> pathogenic allelic variant penetrance. The analysis included 380 DNA samples of women with confirmed positive <italic>BRCA1</italic> status for one of founder variants c.4035del and c.5266dup. The c.444+1G>A and c.470T>C variants of <italic>CHEK2</italic> gene were identified by Sanger’s sequencing, and the del5395 variant was detected by multiplex PCR. The studied <italic>CHEK2</italic> 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.</p>
</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.

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

Pauls Stradiņš Clinical University Hospital

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

This work is licensed under the Creative Commons Attribution 4.0 International License.

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

Germline pathogenic BRCA1 variants confer increased risk of breast and/or ovarian cancer. The penetrance of BRCA1 pathogenic variants is variable due to the...

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

Published Online: May 18, 2023

Page range: 137 - 140

Received: Nov 01, 2021

Accepted: Feb 08, 2023

DOI: https://doi.org/10.2478/prolas-2023-0020

Keywords
pathogenic variant carriers, breast cancer, double heterozygote, ovarian cancer

© 2023 Egija Berga-Švītiņa et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

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

Published Online: May 18, 2023

Page range: 137 - 140

Received: Nov 01, 2021

Accepted: Feb 08, 2023

DOI: https://doi.org/10.2478/prolas-2023-0020

Keywordspathogenic variant carriers, breast cancer, double heterozygote, ovarian cancer

© 2023 Egija Berga-Švītiņa et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Keywords
pathogenic variant carriers, breast cancer, double heterozygote, ovarian cancer