Further, any test designed to leverage BRCA2 status as a biomarker for PCa must consider both germline and somatic mutations and all types of deleterious mutations.
We also discuss guidelines on screening and management for other cancers associated with BRCA1 and BRCA2, such as male breast cancer, pancreatic cancer, and prostate cancer.
Furthermore, we reviewed the 62 PrCa diagnoses in all HBOC (n = 161) and Lynch syndrome (n = 124) families previously diagnosed at our department, and found five other BRCA2 mutation carriers and two additional MSH2 mutation carriers.
For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of B100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B.
We report 8 additional genes with suggestive evidence of association, including the DNA repair genes PARP2 and MSH6 Finally, we observed an excess of rare truncation variants in 5 genes, including the DNA repair genes MSH6, BRCA1, and BRCA2 This adds to the growing body of evidence that DNA repair pathway defects may influence susceptibility to aggressive prostate cancer.
Male mutation carriers and first-degree relatives in BRCA2 families are at an increased risk of breast cancer and prostate cancer with a potential prostate cancer cluster region within exon 11 of BRCA2.
Early phase clinical trials with PARPi have been promising in patients with advanced BRCA1 or BRCA2-associated breast, ovary and prostate cancer and have led to limited approval for treatment of BRCA-deficient ovary cancer.
Exome sequencing was performed on 5 PC-affected men from 3 families where there were multiple cases of PCs and where diagnostic testing returned a negative result for BRCA1 and BRCA2 mutations.
Most notably, HOXB13 and BRCA2 mutations have been consistently shown to increase prostate cancer risk, and are more commonly observed among patients diagnosed with early-onset disease.
In addition, it was recently shown that aberrations in DNA repair genes, such as BRCA2 and ATM, are present in both somatic and germline form in a significant minority of prostate cancer; these abnormalities can be targeted by drugs such as platinums and PARP inhibitors.
To ascertain whether D'Amico risk classification is an accurate discriminator of prostate cancer mortality risk in BRCA2 pathogenic mutation carriers and non-carriers from a familial breast cancer cohort.
Our case underscores the observation that BRCA2 mutation carriers are at risk for multiple cancers, including contralateral breast cancer, and illustrates the need for current practice recommendations for the early detection of breast and prostate cancer in men with BRCA2 mutations.
Individuals with a BRCA2 mutation had significantly higher numbers of observed cases versus expected cases for pancreatic cancer in both men and women (SIR, 21.7; 95% confidence interval [CI], 13.1-34.0; P < .001) and for prostate cancer in men (SIR, 4.9; 95% CI, 2.0-10.1; P = .002).
To investigate the presence and implications of IDC-P in men with a strong family history of PCa who either carry a BRCA2 pathogenic mutation or do not carry the mutation (BRCAX).
Several features previously associated with poor PCa outcome have been found to be significantly more common in BRCA2-mutated PCa than in sporadic tumours and may help to explain their adverse prognosis and be of relevance for targeted therapies.