BRCA1-BRCA2
BRCA1 (BReat CAncer gen 1), BRCA2 (BR east CAncer gene 2) These are the genes that provide protein production for DNA repair, that is, they take part in and manage DNA repair.
These genes consist of 2 copies, one comes from the mother and the other comes from the father. Since these genes perform DNA repair, they are called tumor suppressor genes. A defect in these genes paves the way for the development of cancer, as DNA repair cannot be carried out after a mutation.
People with this genetic mutation are at risk of developing different types of cancer, especially ovarian and breast cancer. People with this mutation may develop cancer at an earlier age.
Individuals with this genetic mutation have a 50% chance of passing the mutation on to their children.
Genetic mutations are seen in all cells in our body when they come from the mother or father at birth. Genetic mutations that occur later are not seen in all cells.
The genetic mutation comes either from the mother or the father. When there is a mutation from both, the embryo cannot develop, that is, the baby cannot be born.
Let's assume that the BRCA mutation comes from the father, in this case the normal BRCA gene comes from the mother and this normal gene repairs DNA and suppresses cancers that may develop, but sometimes due to external effects, there is a change in this normal BRCA gene in some cells (somatic alteration). That's when cancer can occur in these cells that do not have the normal BRCA gene.
How common is breast and ovarian cancer in women with BRCA gene mutation
Breast and ovarian cancer throughout life The risk of cancer increases in BRCA mutation.
Breast cancer: The lifetime risk of breast cancer in women is 13%. This rate is 55-70% in BRCA1 gene mutation and 45-70% in BRCA2 mutation. Women with this mutation have a high risk of developing breast cancer in the opposite breast.
Ovarian cancer: Normally, the risk of ovarian cancer is around 1%, but in BRCA1 mutation, this rate is 40-45% and in BRCA2 mutation. BRCA1-2 mutations also increase the risk of other cancers, for example cancers of the uterine tubes and peritoneum in women, and breast cancer in men. e and prostate cancer risk increases.
BRCA mutation is more common in some ethnicities. There are different variants of BRCA gene mutations, the incidence varies from society to society.
Who should have BRCA1 and BRCA2 tests.
This test It can be applied to anyone who is thought to have a genetic mutation, that is, we have tests that can detect these mutations, but these tests are not routinely applied to everyone, but they are applied to selected people who are thought to have a mutation. When detecting these people, the cancer history in the family is usually questioned, who has which type of cancer and at what age the cancer is diagnosed. determined, these are important guiding information. Those with breast, ovarian, fallopian duct, peritoneal cancer in their family, close relatives, and those with BRCA mutation detected in their family tree should be evaluated for risk and BRCA mutation tests should be performed when necessary.
BRCA mutation tests can be performed on suspected healthy individuals. It is also performed on breast cancer patients with suspected mutation. If a mutation is detected in a patient, tests should be started, starting with first-degree relatives. In this case, genetic counseling should be received from a physician who specializes in breast diseases regarding who will be tested.
There are different types of mutations in the BRCA gene, tests should cover all types of mutations in these genes. For clarity, let's say, for example, that the BRCA mutation test types are yellow, red, blue and green, all of these yellow, red, blue and green mutations are searched for in the risky person, and if only the red mutation is detected as a result of the test, this person's relatives will also be tested for only the red mutation. makes. Other mutations are not sought.
In patients with a BRCA mutation, it should be investigated whether this mutation is a germline (hereditary) mutation or a somatic mutation. This distinction can be made in BRCA tests in the blood.
Among gene tests, other than BRCA, there are tests such as CDH1, PALB2, PTEN, TP53.
BRCA gene tests. - how are mutation test results evaluated:
The test result is positive, negative or the data cannot be evaluated clearly (variant of uncer tain significance-VUS), as a result, there is a genetic mutation, but it has not been determined whether it has a negative effect on health.
Positive result We cannot say that every patient will definitely get cancer, but a positive result in the patient poses a risk for future generations. The risk of BRCA mutation in each child born is 50%. Even if the person with the mutation does not have cancer, their children may develop cancer.
Sometimes, the mother and father of the person with the BRCA mutation may not have the mutation; the mutation is caused by the mutation in the ovum or sperm that forms the embryo. This is called "denovo mutation".
Negative test result is interpreted differently.
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The patient's mother If the patient's father is negative, the test result is also considered negative.
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If the patient's mother, father or first-degree relatives cannot be tested, for example, if they are not alive, the test result is considered uncertain. Because there may be a mutation in any untested gene.
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There may be an error in the test results for technical reasons.
VUS The test result shows that there is a mutation , but this mutation has not been shown to be related to a disease or it is a rare mutation in the society. Since the consequences of this mutation cannot be determined, the patient is followed closely according to the family history of the disease. This test result can be re-evaluated as a result of genetic developments.
How should those with positive BRCA gene mutation be followed up;
The test result is positive. Patients who are diagnosed can be followed up with intensive imaging tests.
They are treated with risk-reducing surgery.
They may receive preventive drug treatment.
Intensive imaging examinations
Breast cancer in patients with BRCA mutation Screenings start at earlier ages (20-25 years old). Mammography and breast MRI are performed alternately at 6-month intervals.
There is no screening method to detect ovarian cancer early.
Breast in men. Cancer screenings start at age 35, Patients should also start PSA tests at age 40 for prostate cancer.
Patients should also be screened for pancreatic cancer.
Surgeries to reduce risk
To reduce the risk, both breast tissues can be removed, and to reduce the risk of ovarian cancer, the ovaries should be removed along with the tubes. Removing the ovaries also reduces the risk of breast cancer. Surgeries reduce the risk, but do not completely prevent cancer, so patients should be followed up after the surgery.
Preventive treatments with drugs
Breast in a patient with a mutation. Medicines such as tamoxifen can be used to reduce the risk of cancer. Drug treatment is applied to patients who do not want to have surgery or who cannot tolerate surgery. These drugs also have some side effects, so they should be used under medical supervision. Birth control pills also reduce the risk of breast cancer.
The effect of detecting BRCA mutations on treatment in a woman diagnosed with breast cancer
BRCA Since DNA repair cannot be done in gene mutations, the effect of cancer drugs such as cisplatin and PARP inhibitors acting on DNA increases positively.
Breast cancers tend to be "triple negative" in those with BRCA1 gene mutation. Cancers are more difficult to treat and have a poorer prognosis than other breast cancers.
In those with a BRCA mutation, it should be investigated whether this mutation is a "germline mutation" or a "somatic mutation". In germline mutation, there is a mutation in all cells in the body, so over time, other cancers may occur in these patients, and the mutation may be inherited to the children of these patients. In somatic mutation, the problem is only in the cells where the mutation is seen, it is not inherited.
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