BRCA Mutation - wikipedia

https://en.wikipedia.org/wiki/BRCA_mutation



A BRCA mutation is a mutation in either of the BRCA1 and BRCA2 genes, which are tumour suppressor genes. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, while others have no proven impact. Harmful mutations in these genes may produce a hereditary breast–ovarian cancer syndrome in affected persons. Only 5-10% of breast cancer cases in women are attributed to BRCA1 and BRCA2 mutations (with BRCA1 mutations being slightly more common than BRCA2 mutations), but the impact on women with the gene mutation is more profound.[2] Women with harmful mutations in either BRCA1 or BRCA2 have a risk of breast cancer that is about five times the normal risk, and a risk of ovarian cancer that is about ten to thirty times normal.[3] The risk of breast and ovarian cancer is higher for women with a high-risk BRCA1 mutation than with a BRCA2 mutation. Having a high-risk mutation does not guarantee that the woman will develop any type of cancer, or imply that any cancer that appears was actually caused by the mutation, rather than some other factor.


High-risk mutations, which disable an important error-free DNA repair process (homology directed repair), significantly increase the person's risk of developing breast cancer, ovarian cancer and certain other cancers. Why BRCA1 and BRCA2 mutations lead preferentially to cancers of the breast and ovary is not known, but lack of BRCA1 function seems to lead to non-functional X-chromosome inactivation. Not all mutations are high-risk; some appear to be harmless variations. The cancer risk associated with any given mutation varies significantly and depends on the exact type and location of the mutation and possibly other individual factors.


Mutations can be inherited from either parent and may be passed on to both sons and daughters. Each child of a genetic carrier, regardless of sex, has a 50% chance of inheriting the mutated gene from the parent who carries the mutation. As a result, half of the people with BRCA gene mutations are male, who would then pass the mutation on to 50% of their offspring, male or female. The risk of BRCA-related breast cancers for men with the mutation is higher than for other men, but still low.[4] However, BRCA mutations can increase the risk of other cancers, such as colon cancer, pancreatic cancer, and prostate cancer.



Male breast cancer[edit]

Men with a BRCA mutation have a dramatically elevated relative risk of developing breast cancer, but because the overall incidence of breast cancer in men is so low, the absolute risk is equal to or lower than the risk for women without a BRCA mutation.[9]: Ch8  Approximately 1% to 2% of men with a BRCA1 mutation will develop breast cancer by age 70. Approximately 6% of men with a BRCA2 mutation will develop breast cancer by age 70, which is approximately equal to the risk for women without a BRCA mutation. Very few men, with or without a predisposing mutation, develop breast cancer before age 50.[9]: Ch8 


Approximately half of men who develop breast cancer have a mutation in a BRCA gene or in one of the other genes associated with hereditary breast–ovarian cancer syndromes.


Breast cancer in men can be treated as successfully as breast cancer in women, but men often ignore the signs and symptoms of cancer, such as a painful area or an unusual swelling, which may be no bigger than a grain of rice, until it has reached a late stage.[9]: Ch8 


Unlike other men, men with a BRCA mutation, especially a BRCA2 mutation, may benefit from professional and self breast exams. Medical imaging is not usually recommended, but because male BRCA2 carriers have a risk of breast cancer that is very similar to the general female population, the standard annual mammogram program can be adapted to these high-risk men.[9]: Ch8 


Other cancers[edit]

Mutations have been associated with increased risk of developing any kind of invasive cancer, including stomach cancer, pancreatic cancer, prostate cancer, and colon cancer.[15] Carriers have the normal risks of developing cancer (and other diseases) associated with increased age, smoking, alcohol consumption, poor diet, lack of exercise, and other known risk factors, plus the additional risk from the genetic mutations and an increased susceptibility to damage from ionizing radiation, including natural background radiation.[9]: 39–50 


Men with BRCA mutations cannot get ovarian cancer, but they may be twice as likely as non-carriers to develop prostate cancer at a younger age.[9]: Ch8  The risk is smaller and disputed for BRCA1 carriers; up to one-third of BRCA2 mutation carriers are expected to develop prostate cancer before age 65. Prostate cancer in BRCA mutation carriers tends to appear a decade earlier than normal, and it tends to be more aggressive than normal. As a result, annual prostate screening, including a digital rectal examination, is appropriate at age 40 among known carriers, rather than age 50.[9]: Ch8 


Cancer of the pancreas tends to run in families, even among BRCA families.[9]: Ch8  A BRCA1 mutation approximately doubles or triples the lifetime risk of developing pancreatic cancer; a BRCA2 mutation triples to quintuples it. Between 4% and 7% of people with pancreatic cancer have a BRCA mutation.[15] However, since pancreatic cancer is relatively rare, people with a BRCA2 mutation probably face an absolute risk of about 5%. Like ovarian cancer, it tends not to produce symptoms in the early, treatable stages. Like prostate cancer, pancreatic cancer associated with a BRCA mutation tends to appear about a decade earlier than non-hereditary cases.[15] Asymptomatic screening is invasive and may be recommended only to BRCA2 carriers who also have a family history of pancreatic cancer.[9]: Ch8 


Melanoma is the most deadly skin cancer, although it is easily cured in the early stages. The normal likelihood of developing melanoma depends on race, the number of moles the person has, family history, age, sex, and how much the person has been exposed to UV radiation. BRCA2 mutation carriers have approximately double or triple the risk that they would normally have, including a higher than average risk of melanoma of the eye.[9]: Ch8 [15]


Cancer of the colon is approximately as common in both men and women in the developed world as breast cancer is among average-risk women, with about 6% of people being diagnosed with it, usually over the age of 50.[9]: Ch8  Like sporadic prostate cancer, it is a multifactorial disease, and is affected by age, diet, and similar factors. BRCA mutation carriers have a higher than average risk of this common cancer, but the risk is not as high as in some other hereditary cancers. The risk might be as high as four times normal in some BRCA1 families, and double the normal risk among BRCA2 carriers. Like pancreatic cancer, it may be that only some BRCA mutations or some BRCA families have the extra risk; unlike other BRCA-caused cancers, it does not appear at an earlier age than usual.[9]: Ch8  Normal colon cancer screening is usually recommended to BRCA mutation carriers.


Mutations in BRCA1 and BRCA2 are strongly implicated in some hematological malignancies. BRCA1 mutations are associated acute myelogenous leukemia and chronic myelogenous leukemia.[16] Mutations of BRCA2 are also found in many T-cell lymphomas and chronic lymphocytic leukemias.[16]





BRCA gene mutations: brca-fact-sheet

https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

National Cancer Institute NIH USA cancer gov


BRCA Gene Mutations: Women Cancer Risk and Genetic Testing







10 THINGS TO KNOW ABOUT BRCA GENES -- Texas oncology

https://www.texasoncology.com/services-and-treatments/genetic-testing/things-to-know-about-brca-genes


Patients are becoming increasingly aware of the BRCA genes. However, many questions still exist about what they are and their link to hereditary breast and ovarian cancer, as well as other cancers. Here are answers to commonly asked questions.







Q: What are the BRCA genes?

The BRCA genes are tumor suppressor genes. They prevent uncontrolled cell growth and abnormal cells from turning into cancer. You have two copies of the BRCA-1 and BRCA-2 gene. If you’re a “BRCA carrier,” you have a mutation, or change, in one of the BRCA genes which prevents it from working properly. These individuals have higher lifetime risks for cancer because the gene is not functioning correctly.



Q: Where do BRCA mutations come from?

BRCA mutations are inherited from a parent and are passed down from generation to generation. If you have a BRCA mutation, you have a 50 percent chance of passing the mutation to each of your children. These mutations do not skip generations but sometimes appear to, because not all people with BRCA mutations develop cancer. Both men and women can have BRCA mutations and can pass them onto their children.



Q: How common are BRCA mutations?

BRCA mutations are rare – affecting about 1 in 400 people. However, individuals of Ashkenazi Jewish decent have about a 1 in 40 chance of having a BRCA mutation. Close to 1 million people in the United States are estimated to have a BRCA mutation, but less than 10 percent are aware that they have a mutation that increases their risk for cancer. That’s why genetic counseling is very important.



Q: What types of cancer do the BRCA genes cause?

Mutations in the BRCA genes cause Hereditary Breast and Ovarian Cancer Syndrome (HBOC). The lifetime risk for breast cancer is estimated to be 55 to 85 percent, and the lifetime risk for ovarian cancer is 27 to 44 percent. Women with a BRCA mutation have higher risks for breast and ovarian cancer. If you’re a BRCA carrier and have already had breast cancer, you have an increased risk for a second breast cancer. BRCA mutations may also increase your risk for prostate, melanoma, and pancreatic cancer.



Q: Do these genes affect men?

Yes. Men are often forgotten in discussions of the “breast” cancer genes. If you’re a man with a BRCA mutation, you have a 20 percent lifetime risk for prostate cancer, a 6 percent lifetime risk for male breast cancer, and elevated risks of pancreatic cancer and melanoma. Men with BRCA mutations also need to have increased cancer screenings.



Q: Is a mastectomy the only option for BRCA carriers?

No. While some women choose to have a bilateral mastectomy, there are other options to reduce your breast cancer risk. These include monthly self-breast exams, clinical breast exams two times a year, as well as annual mammograms, and annual breast MRIs. Chemoprevention, a medication that reduces breast cancer risk, may also be an option for you.


At this time, there are no effective screening techniques for ovarian cancer. High risk patients may consider ultrasounds or a blood test called CA-125, but these tests are not known to be effective at detecting ovarian cancer at an early stage. If you have a BRCA mutation and have finished having children, we recommend having your ovaries and fallopian tubes removed to reduce your risk of ovarian cancer (usually around age 35-40). This procedure, called an oophorectomy, also reduces your risk for breast cancer and has been associated with a 77 percent reduction in your overall risk of death.


Men with BRCA mutation should have increased screening for breast and prostate cancer.


BRCA carriers have many difficult decisions to make, and with that knowledge they can work with healthcare professionals to make sure they make the right decisions for themselves and their family.



Q: Should I get tested and how much does it cost?

While there are many people with BRCA mutations, not everyone needs to be tested to determine if they have a mutation. It’s important to think about your personal and family history to determine if BRCA testing may be right for you. You should consider genetic testing if you have any of these signs of hereditary breast and ovarian cancer:


Ovarian cancer at any age

Breast cancer at age 45 or younger

Two breast cancers in the same woman, one before age 50

Two relatives with breast cancer, with one before age 50

Male breast cancer

Breast cancer at or before age 60 that is “triple negative” or ER, PR, HER2 negative breast cancer

Three or more relatives with breast, ovarian, pancreatic, or aggressive prostate cancer

Ashkenazi Jewish ancestry and a personal or family history of breast, ovarian, or pancreatic cancer

Healthcare providers with specialized training in genetics meet with individuals who have a personal or family history of cancer to determine if genetic testing would be useful. The evaluation usually takes one hour and involves taking a thorough personal and family history, and a discussion of the risks, benefits, and limitations of testing. After this evaluation, if genetic testing is warranted, the healthcare providers can coordinate genetic testing. Once your test results are received, they help create a personalized management plan based on your personal and family history and your test results.


Genetic testing for the BRCA genes is expensive. Comprehensive testing of both genes currently costs about $2,000 -$4,000. Most insurance companies will cover the testing if you have a significant personal and family history.



Q: I’ve already had BRCA testing and it was negative, does that mean my breast cancer is not genetic?

If you’ve had a negative BRCA test, it’s unlikely a mutation in a BRCA-1 or BRCA-2 gene caused your cancer. However, there could be a different genetic cause for your cancer. Each of us has between 20,000-25,000 genes. There are additional breast and ovarian cancer genes that have been discovered, and genetic testing for those also is possible. If you have a significant personal or family history of cancer, we recommend talking with you doctor to determine if additional genetic testing is warranted.



Q: Are other types of cancers inherited?

The majority of cancer is sporadic or something that happens by chance. Approximately 5 to 10 percent of cancers are caused by gene changes that run in a family. The BRCA genes are just two genes that are known to cause hereditary cancer. There are also genes that increase your risk for other types of cancer, including colon cancer, uterine cancer, and ovarian cancer, and others. If you’re concerned about your personal or family history of cancer, ask your doctor if a genetic risk evaluation may be helpful for you.



Q: Where can I learn more?

If you want to learn more about Hereditary Breast and Ovarian Cancer or BRCA mutations visit Facing Our Risk of Cancer Empowered or Bright Pink. You can also learn more about our Genetic Risk Evaluation and Testing Program.