What are BRCA1 and BRCA2 genes?

Genetics

BRCA1 and BRCA2 genes are tumor-suppressor genes that produce proteins that help repair any damage to the genetic information in a cell and halt abnormal cell growth. If these genes are mutated, then the DNA repair function is usually lost. Mutations in the BRCA1 and BRCA2 genes are transmitted in an autosomal dominant pattern in a family. In the early 1990s, it was determined that mutations in the BRCA1 gene, located on chromosome 17, increase the risk of breast cancer. Shortly thereafter, breast cancer was also linked to mutations in the BRCA2 gene, located on chromosome 13. According to the American Cancer Society, about 90 to 95 percent of breast cancers are not caused by inherited changes in genes. For those that are, about 16 percent are due to BRCA1 or BRCA2 mutations, with the remainder due to mutations in the genesATM, TP53, CHEK2, PTEN, CDH1, STK11, NBS1, FANCJ, FANCN, and others as-yet unidentified, as reported in a 2011 Cell Oncology literature review.

Cancer Risk

In addition to an increased risk for breast cancer in men and women, inherited mutations in either of the BRCA genes also significantly increase the risk for a woman to develop ovarian, fallopian tube, or uterine cancer.
Mutations in the BRCA1 gene also increase the risk for prostate cancer in men and for colon cancer, while mutations in the BRCA2 gene have also been linked to increased risk of malignant melanoma; cancers of the pancreas, gallbladder, and stomach; and prostate and breast cancer in men. Estimates of risk for breast cancer by age seventy in women with an altered BRCA1 or BRCA2 gene is 45 to 65 percent, as compared to 12.3 percent for women in the general population, according to a 2013 US Preventive Services Task Force recommendation statement.

Genetic Testing

If a family has a strong history of breast and/or ovarian cancer, genetic testing that identifies mutations in the BRCA genes may be beneficial. A family member who has been diagnosed with breast or ovarian cancer provides a blood sample. DNA sequencing analyzes the DNA pattern of the BRCA1 and BRCA2 genes and compares it to the normal sequence in these genes. If a mutation is found in the DNA sequence of one of these genes, then it is likely that the tested person’s cancer was caused by an altered BRCA gene. Other family members can then be tested for this particular gene change and the risk for that individual developing breast or ovarian cancer can be gauged.

Management and Therapy

Individuals with mutated BRCA1 or BRCA2 genes can manage their increased cancer risk through several approaches. Early diagnosis of breast cancer can be increased through periodic mammography, clinical breast exams, and ultrasound. In some cases, prophylactic surgery is recommended to remove as much of the at-risk tissue as possible. To reduce the risk of developing cancer, or to reduce the risk of cancer reoccurring, chemoprevention (chemotherapy) is often employed. Progress is being made in using gene therapy to repair mutated genes that increase the risk for cancer.

Impact

Identification and isolation of the BRCA1 and BRCA2 genes proved that breast cancer, as well as some other types of cancer, can be inherited. DNA analysis to identify acquired BRCA gene mutations can help doctors more accurately predict survival of women with breast and/or ovarian cancer and implement proper treatment to help control the disease. BRCA gene abnormalities are found among 6 percent of younger women (under the age of forty) who develop breast cancer, according to the US Preventive Services Task Force. Investigation of BRCA gene mutations has not only generated increased interest in breast and ovarian cancer research but also initiated research into using gene therapy as a treatment for cancer and motivated geneticists to escalate their search for genetic-related links as the source of other diseases.

Key Terms




chemoprevention


:

using natural or synthetic chemicals to reduce the risk of developing cancer




DNA

:

deoxyribonucleic acid, the carrier of genetic information in cell nuclei





gene therapy


:

repairing or manipulating genes by insertion of DNA to reduce the risk of cancer





mutation


:

alteration in the normal DNA pattern or chemical sequence along a gene




prophylactic surgery

:

removing tissue that enhances the risk of developing cancer





tumor-suppressor gene


:

genes that control cell growth and cell death





Bibliography

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"BRCA1 and BRCA2 Gene Testing." MedlinePlus. US National Library of Medicine, 20 Sept. 2013. Web. 24 July 2014.

"Breast Cancer Early Detection." Cancer.org. American Cancer Society, 17 Sept. 2013. Web. 24 July 2014.

Greene, Diane Tropea. Apron Strings: Inheriting Courage, Wisdom and . . . Breast Cancer. Highland City: Rainbow, 2007. Print.

Lu, Karen H., ed. Hereditary Gynecologic Cancer: Risk, Prevention and Management. London: Informa HealthCare, 2008. Print.

McPhee, Stephen, Maxine Papadakis, and Michael W. Rabow, eds. Current Medical Diagnosis & Treatment, 2015. 54th ed. New York: McGraw-Hill Medical, 2014. Print.

US Preventive Services Task Force. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement. AHRQ Publication No. 12-05164-EF-2. Rockville: USPSTF Program Office, Dec. 2013. Web. 24 July 2014.

Van der Groep, Petra, Elsken van der Wall, and Paul J. van Diest. "Pathology of Hereditary Breast Cancer." Cell Oncology (2011): 71–88. Web. 24 July 2014.

Zimmerman, Barbara T. Understanding Breast Cancer Genetics. Jackson: UP of Mississippi, 2004. Print.