The human genes BRCA1 and BRCA2 produce tumor suppressor proteins that help repair damaged DNA playing a very important role ensuring the stability of genetic cell material. If the genes are mutated, the proteins will either not be produced or will not be functional. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.
In the general population, approximately 1 in 8 women (12%) will develop breast cancer in their lifetime, and 1 in 75 women (1.4%) will be diagnosed with ovarian cancer in their lifetime (SEER seer.cancer.gov/). Most cases of breast or ovarian cancers develop sporadically with no family history of the cancer. Individual risk factors and exposures, such as age, pregnancy history, menstrual history, benign breast disease, radiation exposure, and alcohol intake, are known to modify a woman’s chance of developing these types of cancers. However, 5-10% of breast cancer cases and 15-20% of ovarian cancer cases are thought to be due to a hereditary predisposition (1,2). BRCA1 ex9-12del seems to be a Mexican founder mutation and represents 10% to 12% of all BRCA1 mutations in clinic- and population-based cohorts in the United States. (3) In Ashkenazi Jews, there is a high population frequency (approximately 2%) of three founder mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT (4). This test is aimed to target these variations. Important to mention that the variation had been found in other non-Jewish ethnic groups such as: Austrian, Slovenian, Spanish, German, Czech, Hungarian, Greek Danish, Polish, Latvian, Lithuanian, Belarusian, Russian. (5)
BRCA Mutations | |||
---|---|---|---|
BRCA Gene | Mutation Name | SNP Number | Gene Position |
BRCA1 | c.68_69 delAG | rs386833395 | Exon 2 |
BRCA1 | c.5263_5264 insC | rs80357906 | Exon 20 |
BRCA2 | c.5946 delT | rs80359550 | Exon 11 |
Soon the full sequence of BRCA1 and BRCA2 will be available.
The analysis of common variants in the BRCA1 and BRCA2 genes is detected by automated DNA sequencing. The gene is analyzed by PCR-based double-stranded automated sequencing in the sense and antisense directions.
Specimen Rejection Criteria: Below are general rejection criteria. If the specimen must be rejected based on the following criteria, or specific criteria for the requested test:
1. Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer. 1996;77(11):2318–2324.
2. Pal T, Permuth-Wey J, Holtje T, Sutphen R. BRCA1 and BRCA2 mutations in a study of African American breast cancer patients. Cancer Epidemiol Biomarkers Prev. 2004;13(11 pt 1):1683–1686.
3. Weitzel JN, Lagos VI, Herzog JS, et al. Evidence for common ancestral origin of a recurring BRCA1 genomic rearrangement identified in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev. 2007;16:1615–1620.
4. Levy-Lahad E, Catane R, Eisenberg S, et al. Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. American Journal of Human Genetics. 1997;60(5):1059-1067.
5. Janavičius R. Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. The EPMA Journal. 2010;1(3):397-412. doi:10.1007/s13167-010-0037-y.