Germline mutations occurring in the highly penetrant genes BRCA1 and BRCA2 are responsible for only certain cases of familial breast cancer (BC) and ovarian cancer (OC).
Probability of breast/ovarian cancer development is higher in individuals carrying a causative germline DNA variant in BRCA1 or BRCA2 gene responsible for hereditary breast/ovarian cancer (HBOC).
Loss of heterozygosity, somatic point mutations and copy number alterations along with promoter methylation were studied in 56 breast and 15 ovarian cancers from BRCA1 and BRCA2 germline mutation carriers.
There were 5712 women tested for a BRCA1 and BRCA2 mutation at the HCP between 2001 and 2014, 887 of which had previously received a diagnosis of ovarian cancer.
The role of both germ line and somatic mutations in BRCA1 and BRCA2 in the development of ovarian cancer is well established, with mutation in either gene resulting in deficiencies in homologous recombination.
This prospective study suggests that tobacco smoking is associated with a modest increase in the risks of breast and ovarian cancer among women with BRCA1 or BRCA2 mutation.
Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have shown an impressive safety profile and anti-tumor efficacy in patients with breast cancer 1 and 2 (BRCA1 and BRCA2) gene-mutated ovarian cancer who were previously treated with the standard of care chemotherapy.
The primary aim of this study was to determine which factors influence the intent of individuals with a personal history of breast and/or ovarian cancer and negative or uncertain BRCA1 and BRCA2 testing to return to a hereditary cancer program for additional genetic risk assessment, counseling, and testing.
After adjusting for mutation position, association between FH and OC risks was slightly smaller in magnitude (HR: 0.85, 95% CI: 0.55-1.30; HR: 0.64, 95% CI: 0.34-1.21 for BC-only FH in BRCA1 and BRCA2, respectively; HR: 1.46, 95% CI: 0.80-2.68; HR: 1.49, 95% CI: 0.44-4.02 for OC-only FH in BRCA1 and BRCA2, respectively), indicating that mutation position explains only part of the association.
Pathogenic variants in BRCA1 or BRCA2 are identified in ∼20% of families with multiple individuals affected by early-onset breast and/or ovarian cancer.
Finally, neurofibromin 1, synaptonemal complex protein 2 and tumor protein 53 were predicted to be involved in the interaction network of BRCA1 and BRCA2 in breast cancer and ovarian cancer.
Monoallelic inactivation of some FA genes, such as FA complementation group D1 (FANCD1; also known as the breast and ovarian cancer susceptibility gene BRCA2), leads to adult-onset cancer predisposition but does not cause FA, and somatic mutations in FA genes occur in cancers in the general population.
Our results indicate that different types of mutational events in the BRCA1 and BRCA2 genes are responsible for the hereditary component of breast/ovarian cancer in the Greek population.
For some time, it has been clear that key mutations may be used as both prognostic and predictive biomarkers, the best-known examples being the presence of germline BRCA1 or BRCA2 mutations, which are not only associated with improved prognosis in ovarian cancer, but are also predictive of response to poly(ADP-ribose) polymerase (PARP) inhibitors.
BRCA2, a cancer susceptibility gene, has been widely studied in breast and ovarian carcinomas as mutation carriers for this gene are at a high risk for cancer development.