These results suggest that BRCA2 is a tumor suppressor gene and may be involved in the tumorigenesis of several cancer types in addition to breast cancer.
The same BRCA2 mutation appears to be associated with different cancer phenotypes in this population including male and female breast cancer, prostate cancer, pancreas cancer and ovarian cancer.
Here, we report the frequency of the 999del5BRCA2 mutation in an Icelandic control population and four different groups of cancer patients diagnosed with (a) breast cancer; (b) ovarian cancer; (c) prostate cancer (patients younger than 65 years); and (d) other cancer types.
Combined with our demonstration of BRCA2 expression in adult liver tissue, the evidence implies that inactivation of BRCA2 may play some role in development or progression of hepatocellular carcinoma and might predispose carriers of mutant alleles to liver malignancies.
A family history of pancreatic adenocarcinoma is not common in patients with this disease, but recent research has shown that pancreatic adenocarcinoma can be a feature of cancer susceptibility syndromes associated with germline mutations in p16, BRCA1, BRCA2, and APC.
Only one of the two male breast cancer patients carrying a BRCA2 mutation had a family history of cancer, with one case of ovarian cancer in a first-degree relative.
BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops.
The practical examples are restricted to a few cancer types, but the identification of new tumor suppressor genes, like BRCA-1 and BRCA-2, is creating new possibilities for determining cancer risk of individual family members.
Since the combined frequency of BRCA1 and BRCA2 mutations exceeds 2 percent among Ashkenazi Jews, we were able to estimate the risk of cancer in a large group of Jewish men and women from the Washington, D.C., area.
We calculated that, on average, 30-year-old women who carry BRCA1 or BRCA2 mutations gain from 2.9 to 5.3 years of life expectancy from prophylactic mastectomy and from 0.3 to 1.7 years of life expectancy from prophylactic oophorectomy, depending on their cumulative risk of cancer.
BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2.
Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life.
Our purpose was to determine the prevalence of BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in a large, unselected population of ovarian cancer patients and to evaluate the relationship between mutation status and a routinely obtained family history of cancer.
Germline mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 have been linked to the development of breast cancer, ovarian cancer, and other malignancies.
Individuals in cancer-prone kindreds are currently being screened for germline mutations in BRCA1, BRCA2, and several MMR genes (eg, MSH2, MLH1), and mutant allele carriers counseled for cancer risks.
The presence of a P53 mutation in 80% of these cancers indicates that P53 mutation is common but not required for BRCA-linked ovarian tumorigenesis; notably, a significantly higher proportion of the P53 mutations in BRCA2-linked cancers were deletions or insertions compared with the more typical spectrum of missense mutations seen in BRCA1-linked cancers.
Following the genomic localization and subsequent identification of the breast cancer susceptibility genes, BRCA1 and BRCA2, the basic patterns of cancer risk associated with mutations in these genes have been defined.