In this commentary, we review the current literature and hypotheses surrounding the relationship between BRCA2 mutations and susceptibility to prostate cancer and speculate on the potential for involvement of additional genes.
Under the assumption that LOH occurs only because the cancer was caused by the germline mutation, carriers of BRCA2 mutations are at 3.5-fold (95% confidence interval, 1.8-12) increased risk of prostate cancer.
Mutations in BRCA2 have been associated with increased prostate cancer risk and account for around 2% of young onset (<56 years) prostate cancer cases.
We report here an evaluation of the impact on relatives of being informed of study results that detected pathogenic BRCA2 mutations in a male relative, now deceased, who had early onset (under the age of 55) prostate cancer.
Several epidemiologic studies have reported that carriers of germline mutations in the BRCA2 gene have an increased risk of prostate cancer, with the highest risk observed in men diagnosed at earlier ages.
Germ line mutations in several genes (BRCA1, BRCA2, and CHEK2) whose products are involved in the DNA damage-signaling pathway have been implicated in prostate cancer risk.
Chromosomal deletion is frequent at the region between BRCA2 and RB1 in the q14 band of chromosome 13 (13q14) in human cancers, including prostate cancer, suggesting the presence of a tumor suppressor gene.
In summary, these results unravel a novel mechanism whereby prostate carcinoma cell proliferation is enhanced by the down-regulation of BRCA2 expression when interacting with COL1, a major component of the ECM at osseous metastatic sites.
Male BRCA1 and BRCA2 mutation carriers: a pilot study investigating medical characteristics of patients participating in a prostate cancer prevention clinic.
Extending the model to include (1) prostate cancer, (2) two mutated alleles of BRCA2, namely, mutations in Ovarian Cancer Cluster Region (OCCR) and non-OCCR region, and (3) relatives of degree greater than second-degree, leads to different carrier probabilities.
Inherited mutations of the BRCA2 gene give rise to a multi-site cancer phenotype which includes breast cancer (in female and males), ovarian, pancreatic and prostate cancer, ocular and other melanomas, laryngeal, colon and stomach cancers.
The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations.
It is also of interest to mention that a significant percentage of men with early-onset prostate cancer harbor germline mutation in the BRCA2 gene thus confirming its role as a high-risk prostate cancer susceptibility gene.
These results confirm that BRCA2 is a high-risk prostate-cancer-susceptibility gene and have potential implications for the management of early-onset prostate cancer, in both patients and their relatives.
Relatives of BRCA1 and BRCA2 mutation carriers have long been proposed by epidemiological studies to have an increased risk of developing prostate cancer.