Purpose: Hereditary breast/ovarian cancer (HBOC) occurs in families with several members affected. Most HBOC is caused by mutations in high penetrance BRCA genes accounting for about 5% of all breast cancers. There is a large number of genes with moderate or low penetrance, contributing to non-BRCA aggregation of breast and ovarian cancers. In the present study, we evaluated the presence and frequency of 1100delC and Del5395 mutations in CHEK2 gene in Serbian BRCA-negative HBOC cases.
Methods: We analyzed 57 BRCA-negative subjects from high risk breast/ovarian cancer families from Serbia for CHEK2 1100delC and Del5395 mutations. We used two multiplex allele specific PCR in order to detect them. All suspected positive cases were compared with controls and confirmed by DNA sequencing.
Results: 1100delC was not detected in the tested group. However, we detected one Del5395 mutation in a female diagnosed with breast cancer at the age of 32 and with apparent family history of breast cancer (her mother and sister were diagnosed with breast cancer at 42 and 39 years of age, respectively). The frequency of Del5395 mutation in our tested group was 1.7% (1/57).
Conclusions: 1100delC variant in CHEK2 gene was not present in the tested subjects from HBOC families in Serbia. However, the finding of Del5395 mutation does not allow us to discard a possible involvement of this gene in breast cancer susceptibility in Serbian population. It would be of great interest to assess the distribution of this large deletion in other countries from the Balkan region in order to assess its geographical distribution and possible founder effect.