Читать книгу Constitutional Oncogenetics - Noureddine Boukhatem - Страница 32

Some genotype–phenotype correlations have been identified in families carrying BRCA2 pathogenic variants.

In studies totaling 189 families with pathogenic variants of BRCA2, an ovarian cancer cluster region was identified in exon 11 between nucleotides 3035 and 6629.

Pathogenic variants in the ovarian cancer cluster region were associated with an increased risk of ovarian cancer and a decreased risk of breast cancer compared to families with variants on either side of this region.

In addition, a study confirmed by other studies involving 356 families with truncated protein pathogenic variants of BRCA1 showed that the risk of breast cancer was lower with variants from the central region (nucleotides 2401–4190). The risk of ovarian cancer was significantly reduced with variants in the 3’ end region of the gene at nucleotide 4191.

Higher rates of ovarian cancer have been found in BRCA1:185delAG carriers at the 5’ end of BRCA1 compared to BRCA1:5382insC carriers at the 3’ end of the gene.

The risk of breast cancer, particularly bilateral breast cancer, and the occurrence of breast and ovarian cancer in the same individual appear to be higher in carriers of the pathogenic variant BRCA1:5382insC than in carriers of BRCA1:185delAG and BRCA2:6174delT. The risk of ovarian cancer is significantly higher in BRCA1 pathogenic variant carriers, and is rare before age 45 in BRCA2:6174delT carriers.