Breast carcinoma is the most common malignancy among women in developed countries and family history remains the strongest single predictor of breast cancer risk. Mutations in the BRCA1 and BRCA2 genes are linked to a high risk of young-onset breast cancer, and appear to be responsible for approximately 10% of total breast cancer cases. Women with these mutations have a cumulative risk of developing breast cancer (up to age 70) of 55-85%. The BRCA1 and BRCA2 proteins are associated with the activation of double-strand break repair and/or homologous recombination. Unlike BRCA1, BRCA2 has not been linked to ovarian cancer. BRCA2 mutations are less frequent than BRCA1 mutations but in families with male breast cancer cases, BRCA2 mutations may be more frequent.
The P045-B3 probemix contains probes for all exons of the BRCA2 gene (13q12.3). Two probes are present for exons 1, 3 and 27, and for the large exon 11. For a reference, 8 probes for other human genes located on different chromosomes are included. In addition, two probes are present for sequences just before and after the BRCA2 gene. Furthermore, three probes for the CHEK2 gene on 22q12.1 are included. One of these probes will only result in an amplification product in case the DNA sample contains the CHEK2 1100delC mutation. The 1100delC allele appears to result in a two fold increase of breast cancer risk in woman and a 10-fold increase of risk in men. The 1100delC allele has been found in the Netherlands in 1.1% of healthy individuals and in 5.1% of individuals with breast cancer, including 13.5% of individuals from families with male breast cancer.