BRCA1 and BRCA2 genes
BRCA1 and BRCA2 are genes that play a crucial role in the body's ability to repair damaged DNA and regulate cell growth, thereby helping to prevent the development of certain cancers. Mutations in these genes significantly increase the risk of breast and ovarian cancer, with estimates suggesting that women with these mutations face a lifetime breast cancer risk exceeding 60%, compared to about 13% for the general population. Inherited mutations can also elevate the risk for male breast cancer, prostate cancer, and other cancers such as pancreatic and colorectal cancer. Genetic testing can identify these mutations, particularly in families with a strong history of breast or ovarian cancer, allowing individuals to understand their risks and make informed decisions regarding monitoring and preventative strategies. Management options for those carrying BRCA mutations include regular screenings, preventive surgeries, and chemoprevention methods to mitigate cancer risk. The discovery and understanding of BRCA1 and BRCA2 have significantly impacted cancer research and treatment approaches, including the exploration of gene therapy as a potential solution for managing cancer risks. Overall, knowledge of these genes is vital for personal health decisions and advancing cancer research.
BRCA1 and BRCA2 genes
SIGNIFICANCE:Risk of breast cancer, the second most common cancer found in women in the United States, can be inherited. BRCA1 and BRCA2 are two genes linked directly with susceptibility to developing breast cancer, as well as to developing ovarian, prostate, and other types of cancer. Mutations in these genes can eliminate their ability to control cell growth.
Genetics
BRCA1 and BRCA2 genes are 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 genes that can cause breast and/or ovarian cancer. According to the National Cancer Institute in 2024, these genes included PTEN, PALB2, TP53, CDH1, and STK11. Other genes that were associated with increased cancer or gynecological cancer risk included CHEK2, BRIP1, RAD51C, RAD51D, and ATM.
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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. The risk for breast cancer with an altered BRCA1 or BRCA2 gene was more than 60 percent during a woman's lifetime, as compared to 13 percent for women in the general population, according to 2024 statistics from the National Cancer Institute.
Genetic Testing
If a family has a strong history of breast and/or ovarian cancer, 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 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
- chemopreventionusing natural or synthetic chemicals to reduce the risk of developing cancer
- DNAdeoxyribonucleic acid, the carrier of genetic information in cell nuclei
- gene therapyrepairing or manipulating genes by insertion of DNA to reduce the risk of cancer
- mutationalteration in the normal DNA pattern or chemical sequence along a gene
- prophylactic surgeryremoving tissue that enhances the risk of developing cancer
- tumor-suppressor genegenes that control cell growth and cell death
Bibliography
"BRCA Gene Changes: Cancer Risk and Genetic Testing." National Cancer Institute, 14 July 2024, www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Accessed 5 Sept. 2024.
"BRCA Genetic Test." MedlinePlus, 12 Sept. 2022, medlineplus.gov/lab-tests/brca-test/. Accessed 5 Sept. 2024.
"Breast Cancer Early Detection and Diagnosis." American Cancer Society, 2024, www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection.html. Accessed 5 Sept. 2024.
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.
"BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing: U.S. Preventive Services Task Force Final Recommendation Statement." US Preventive Services Task Force, 20 Aug. 2019, www.uspreventiveservicestaskforce.org/uspstf/recommendation/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing. Accessed 5 Sept. 2024.
Zimmerman, Barbara T. Understanding Breast Cancer Genetics. Jackson: UP of Mississippi, 2004. Print.