BRCA Genes: Linking Breast, Ovarian, and Prostate Cancer
September is Ovarian and Prostate Cancer Awareness Month, but that isn’t the only link between these two forms of cancer. Inherited changes in the BRCA genes are associated with a significant increase in risk for cancer in several cell types, including, but not limited to, ovarian and prostate cells.
What are genes and how can they cause cancer?
All living things are made of cells. Humans have many different cell types, but each cell contains a central core, called the nucleus. The human nucleus contains a copy of, typically, 23 pairs of chromosomes. The chromosomes are thread-like structures which include the instructions, DNA, required to provide each cell with the information it needs to successfully play its role within the human body. Short sections of DNA that encode for a specific product are called genes. Typically, we have two copies of each gene, one that comes from mom and the second copy that comes from dad that we receive upon conception. Genes determine how an individual’s body grows, develops, and heals. Genetic variations, or changes, within these genes are natural-- it’s what makes us unique! But when certain genes have missing or altered information, it can prevent the gene from working properly and impact how the body functions. These variations that cause disease are known as pathogenic genetic variants. Genes associated with cancer provide the body with instructions to protect us from getting a specific type of cancer. If one of these genes does not function properly, our cells have an increased chance of growing out of control. This erratic growth can become malignant growth, the root of cancers.
What are BRCA Genes and What do they do?
For non-genetics professionals, initial recognition of “BRCA” genes and the association with breast cancer may be through association with actress Angelina Jolie and her openness regarding undergoing a prophylactic double mastectomy, (a surgical procedure to remove a person’s breast tissue to prevent breast cancer), due to her increased genetic risk for breast cancer.
BRCA is the acronym for “Breast Cancer Genes” which include two genes, BRCA1, located on chromosome 17, and BRCA2, located on chromosome 13. When healthy, each of the BRCA genes plays a major role in repairing day-to-day damage incurred in our cells.
What Cancers are Associated with BRCA Genes?
Pathogenic variants in BRCA1 and BRCA2 are associated with breast cancer in both women and men, as well as ovarian, fallopian tube, peritoneal, prostate, and pancreatic cancers. BRCA2 variants are also associated with an elevated risk of melanoma. Rarely, when an individual has a pathogenic variant in each of the two copies of the BRCA2 gene they received from each parent, it causes a form of Fanconi Anemia, which has an extremely high risk of childhood cancers like Acute Myeloid Leukemia, brain cancers, and other malignancies (Alter, et al.; Petrucelli, et al.).
Who May Benefit from Genetic Counseling?
Individuals with family histories of cancer may not realize that patterns of certain cancer types within a family can create a pattern observable by genetics specialists that can help guide both preventative, and active treatment decisions.
Seeking genetic counseling does not start with the desire to pursue testing, but rather the decision to have a professional evaluate your genetic risk factors and provide options and resources if testing is recommended or desired.
Testing is often recommended based on a combination of the following criteria:
A family history of ovarian cancer, breast cancer, metastatic prostate cancer, pancreatic cancer, and particularly, multiple cases of any of these associated cancers concentrated to a single family member or side of the family.
A personal history of breast, ovarian, fallopian, peritoneal, pancreatic, and/or prostate cancers.
A personal or family history of any one of the associated cancers combined with Ashkenazi Jewish ancestry.
When deciding to pursue genetic testing, it is important to keep in mind that BRCA1 and BRCA2 are not the only genes that can cause other inherited cancer syndromes. Different hereditary cancer syndromes associated with increased risk of breast cancer may have increased risks for cancers in different organs than the BRCA associated cancers, so thorough discussion of what genetic testing should be ordered is a critical aspect of preventative health. Genetic counselors will help determine what panel of genetic testing is appropriate based on your family history and the genes known to be associated with specific forms of cancer. For those who do not know their family history, genetic cancer screening panels for the most common syndromes may be curated through these genetic counselor consultations.
What Happens After Risk Assessment?
Most of the time, a specific gene associated with an increased risk for cancer is not found, and healthy lifestyle behaviors and regular or increased preventative care is the best choice of action. For those individuals that identify a known disease-causing gene through genetic testing, there are many, often lifesaving, options that can be taken to give patients the best possible outcomes.
The following standard of care is recommended by the National Comprehensive Cancer Network (NCCN) for patients with disease-causing variations in either of the BRCA genes:
Breast Cancer Prevention:
Monthly breast self-examinations
Clinical breast examinations biannually beginning at age 25
Annual breast MRI beginning at age 25
Annual mammogram beginning at age 30
If possible, breastfeeding for at least a year cumulatively is associated with a reduction of risk for breast cancer
Consideration of prophylactic bilateral mastectomy
Preventative drugs to reduce breast cancer risk
Ovarian Cancer Prevention
Recommendation to use of oral contraceptives to reduce ovarian cancer risk
Recommendation for prophylactic oophorectomy and salpingectomy after childbearing is complete or age 30-40
Ovarian cancer often has no symptoms until it has become highly invasive, which is why the removal of the ovaries and fallopian tubes is recommended as the standard of care after child-bearing is complete
Familial testing in other direct relatives
Smoking cessation
Baseline evaluations for melanoma and increased UV protection measures
Although the National Comprehensive Cancer Network states there is uncertain benefit, some clinicians may recommend annual transvaginal ultrasound and CA-125 bloodwork to check for ovarian cancer in those with ovaries
Prostate Cancer Prevention
Annual prostate exams beginning at age 40
PLA bloodwork accompanying regular prostate exams
Prostate cancer often has no symptoms until it has become highly invasive, which is why proactive preventative screening is the best course of action
Pancreatic Cancer Prevention
There are currently no additional screenings recommended for pancreatic cancer in those with BRCA variants but seeing a physician at any signs of weight loss, unexplained abdominal pain, weight loss, or dietary changes can prevent delays in pancreatic cancer detection.
This September, be reminded to update your family history to include any known cancer occurrences. It may seem like there is a lot of information to keep track of when discussing inherited cancers, but if you are worried, know that you can reach out to your physician or schedule an appointment with a genetic counselor to discuss your risk for hereditary cancer.
The Society of Gynecologic Oncology (SGO) recommends genetic counseling be offered to all women with a personal or family history of ovarian, fallopian tube, and peritoneal carcinomas
Patients with a family history of a first degree relative with breast or ovarian cancer automatically meet qualifications for insurance coverage of voluntary genetic testing for associated risk genes as determined by a genetics professional.
If you notice any changes to your health including abnormal pains, lumps, sores, moles, changes in bleeding or discharge, changes in frequency of urination, contact your physician as soon as possible.
Citations:
Alter, B. P., Rosenberg, P. S., & Brody, L. C. (2007). Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. Journal of medical genetics, 44(1), 1–9. https://doi.org/10.1136/jmg.2006.043257
https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet
D'Andrea A. D. (2013). BRCA1: a missing link in the Fanconi anemia/BRCA pathway. Cancer discovery, 3(4), 376–378. https://doi.org/10.1158/2159-8290.CD-13-0044
Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2016 Dec 15]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1247/
Loizidou, Maria A et al. “Fanconi anemia-D1 due to homozygosity for the BRCA2 gene Cypriot founder mutation: A case report.” Oncology letters vol. 11,1 (2016): 471-473. doi:10.3892/ol.2015.3852
Wu, et al. “The role of BRCA1 in DNA damage response.” NIH Public Access. Protein Cell. 2010 February ; 1(2): 117–123. doi:10.1007/s13238-010-0010-5.
Wu, J., Lu, LY. & Yu, X. The role of BRCA1 in DNA damage response. Protein Cell 1, 117–123 (2010). https://doi.org/10.1007/s13238-010-0010-5 https://www.ncbi.nlm.nih.gov/pmc/articles/mid/NIHMS263012/
“Genetic Testing for Ovarian Cancer.” Society of Gynecologic Oncology, Society of Gynecologic Oncology, 2 June 2020, www.sgo.org/resources/genetic-testing-for-ovarian-cancer/.
My Gene Counsel. “Your Checklist for Ovarian Cancer Genetic Counseling.” My Gene Counsel, Genetic Journal Blog, 31 Aug. 2020, www.mygenecounsel.com/your-checklist-for-ovarian-cancer-genetic-counseling/.
NCCN Guidelines Version 1.2022 “Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic” 2021.
“Signs and Symptoms of Pancreatic Cancer.” American Cancer Society, American Cancer Society Medical and Editorial Content Team, 11 Feb. 2019, www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/signs-and-symptoms.html.