What are BRCA1 and BRCA2?
What are BRCA1 and BRCA2?BRCA1 and BRCA2 genes are the most prominent genes that determine the genetic susceptibility of breast cancer. BRCA1 test and BRCA2 test are the most important tests that measure a person’s genetic susceptibility to breast cancer.
BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. These proteins help repair damaged DNA and therefore play a role in maintaining the stability of the cell’s genetic material. If any of these genes are mutated or changed, the protein product is either not produced or does not function properly, and DNA damage cannot be properly repaired. As a result, cells are more likely to develop additional genetic changes that can lead to cancer.
Inherited mutations specific to BRCA1 and BRCA2 increase female breast and ovarian cancer risk and have been associated with an increased risk of several additional types of cancer. Together, the BRCA1 and BRCA 2 mutations account for about 20 to 25 percent of heredity for breast cancer and about 5 to 10 percent of all breast cancers. In addition, mutations in BRCA1 and BRCA2 account for about 15 percent of ovarian cancers overall. Breast and ovarian cancer associated with BRCA1 and BRCA2 mutations tend to develop at a younger age than their extramarital counterparts.
A harmful BRCA1 or BRCA2 mutation can be inherited from a person’s mother or father. Each child of a parent who has a mutation in one of these genes has a 50 percent chance of inheriting the mutation. The effects of mutations in BRCA1 and BRCA2 are seen even when a person’s second copy of the gene is normal.
Does having a BRCA1 or BRCA2 gene mutation increase a woman’s risk of breast and ovarian cancer?
A woman’s risk of developing breast and/or ovarian cancer is greatly increased if she has a harmful mutation in BRCA1 or BRCA2.
Breast cancer:
About 12 percent of women in the general population will develop breast cancer at some time in their lives. According to the most recent estimates, between 55 and 65 percent of women who inherit a harmful BRCA1 mutation and about 45 percent of women who inherit a harmful BRCA2 mutation will have breast cancer by age 70.
Ovarian cancer:
About 1.3 percent of women in the general population will develop ovarian cancer in their lifetime. According to the most recent estimates, 39 percent of women who inherit a harmful BRCA1 mutation and 11 to 17 percent of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70.
It is important to note that these lifetime risk percentages differ from those previously available; Estimates changed as more information became available and may change again with additional research. Long-term general population studies have not directly compared cancer risk in tumors with and without deleterious BRCA1 or BRCA2 mutations.
It’s also worth noting that other characteristics of a given woman’s cancer risk may be higher or lower than the average risks. These features include a family history of breast, ovarian and possibly other cancers; the specific mutation(s) it inherits; and other risk factors such as reproductive history. However, based on current data, none of these other factors appear to be as effective as carrying a deleterious BRCA1 or BRCA2 mutation.
What cancers are other mutations in BRCA1 and BRCA2 associated with?
Harmful mutations in BRCA1 and BRCA2 increase the risk of several cancers, as well as breast and ovarian cancer. BRCA1 mutations can increase a woman’s risk of developing fallopian tube cancer and peritoneal cancer. Men with BRCA2 mutations and, to a lesser extent, BRCA1 mutations are also at increased risk of breast cancer. Men with harmful BRCA1 or BRCA2 mutations are at increased risk of prostate cancer. Men and women with BRCA1 or BRCA2 mutations may be at increased risk of pancreatic cancer. Mutations in BRCA2 (also known as FANCD1), if inherited from both parents, can result in a Fanconi anemia subtype (FA-D1), a syndrome associated with the development of childhood solid tumors and acute myeloid leukemia. Likewise, mutations in BRCA1 (also known as FANCS) can cause another subtype of Fanconi anemia if inherited from both parents.
Are mutations in BRCA1 and BRCA2 more common in some racial/ethnic populations than others?
Yes. For example, people of Ashkenazi Jewish descent have a higher prevalence of BRCA1 and BRCA2 mutations than people in the general US population. Other ethnic and geographic populations around the world, such as the Norwegian, Dutch, and Icelandic peoples, have a higher prevalence of specifically harmful BRCA1 and BRCA2 mutations.
In addition, limited data suggest that the prevalence of certain deleterious BRCA1 and BRCA2 mutations may differ among individual racial and ethnic groups in the United States, including African Americans, Hispanics, Asian Americans, and non-Hispanic whites.
Are there genetic tests to detect BRCA1 and BRCA2 mutations?
Yes, BRCA1 Test and BRCA2 Test are performed in Istanbul Laboratories.
Many different tests are available, including tests that look for a known mutation in a gene (a previously identified mutation in another family member) and tests that check for all possible mutations in both genes. DNA (from a blood or saliva sample) is required for mutation testing. It takes about a month to get test results.
Who should consider having the BRCA1 Test and the BRCA2 Test?
Because harmful BRCA1 and BRCA2 gene mutations are relatively rare in the general population, most experts agree that mutation testing in individuals without cancer should only be performed if the individual or family history of the person suggests a possible harmful mutation in BRCA1.
The United States Preventive Services Task Force recommended in December 2013 that women with family members with breast, ovarian, fallopian tube, or peritoneal cancer be evaluated to see if their family history is associated with an increased risk of a harmful mutation in one of these genes.
Various screening tools are available to assist healthcare providers with this assessment. These tools assess family history factors associated with an increased likelihood of inheriting a deleterious mutation in BRCA1 or BRCA2; these include:
- Breast cancer diagnosed before age 50
- Two breast cancers in the same woman
- Breast cancer and ovarian cancer in the same woman and in the same family
- Multiple breast cancer
- Two or more primary cancer types related to BRCA1 or BRCA2 in a single family member
- Male breast cancer cases
When an individual has a family history that implies the presence of a BRCA1 or BRCA2 mutation, the BRCA1 Test / BRCA2 Test can be informative to a family member with a cancer who is still alive and willing to be tested. If this person is found to have a harmful BRCA1 or BRCA2 mutation, other family members may consider genetic counseling to learn more about their potential risks and consider whether genetic testing for mutations in BRCA1 and BRCA2 would be appropriate for them.
If it is not possible to confirm the presence of a deleterious BRCA1 or BRCA2 mutation in a family member with cancer, it is appropriate for both men and women who are not cancerous but have a family medical history that indicates the presence of such a mutation, with genetic counseling for possible testing.
Some individuals, such as those admitted at birth, may not know their family history. If a woman with an unknown family history has early-onset breast or ovarian cancer, or a man with an unknown family history of breast cancer is diagnosed with breast cancer, it may make sense for that individual to consider genetic testing for a BRCA1 or BRCA2 mutation. People with an unknown family history without early-onset cancer or male breast cancer are at very low risk of having a harmful BRCA1 or BRCA2 mutation and are unlikely to benefit from routine genetic testing.
Professional societies do not recommend genetic testing for BRCA1 or BRCA2 in children with a family history of implied harmful BRCA1 or BRCA2 mutations. This is because there are no risk reduction strategies for children and the risk of developing a type of cancer associated with a BRCA1 or BRCA2 mutation in children is very low. However, children with a family history of implying a harmful BRCA1 or BRCA2 mutation may wish to seek genetic counseling about whether to undergo genetic testing after they become adults.
Should people considering genetic testing for BRCA1 and BRCA2 mutations see a genetic counselor?
Genetic counseling is usually recommended before and after any genetic testing for an inherited cancer syndrome. This consultation should be done by a healthcare professional with experience in cancer genetics. Genetic counseling usually covers many aspects of the testing process, including:
- An inherited cancer risk assessment based on a person’s personal and family medical history
- Relevance of genetic testing
- Medical consequences of a positive or negative test result
- The possibility that a test result may not be informative
- Psychological risks and benefits of genetic test results
- Risk of passing a mutation to children
- Explanation of the specific test(s) that may be used and the technical accuracy of the test(s)
How much does the BRCA1 and BRCA2 mutation test cost?
The Ministry of Health has not yet considered genetic counseling and BRCA1 and BRCA2 mutation tests as a preventive measure for individuals at high risk. People considering BRCA1 and BRCA2 mutation testing should know before starting the test that they are not covered by the SSI for genetic testing and should consider the high cost.
As a genetic testing laboratory that tests for BRCA1 and BRCA2 mutations, we work in pairs for BRCA 1 -BRCA 2 tests between 2500-3500 TL for patients who have SSI insurance and meet certain financial and medical criteria. For price information, you can call our call center at 444 7 522.
What does a positive BRCA1 or BRCA2 genetic test result mean?
Testing for BRCA1 and BRCA2 gene mutations can yield several possible results: a positive result, a negative result, or an uncertain or uncertain result.
A positive test result indicates that a person has a known harmful mutation in BRCA1 or BRCA2 and is therefore at high risk of developing certain cancers. However, a positive test result does not tell whether or when a person will actually develop cancer. For example, some women who inherit a harmful BRCA1 or BRCA2 mutation may never develop breast cancer or ovarian cancer.
A positive genetic test result can have significant health and social implications for family members, including future generations. Unlike most other medical tests, genetic testing can reveal information not only about the person being tested, but also about that person’s relatives:
Both men and women who inherit a harmful BRCA1 or BRCA2 mutation can pass the mutation on to sons and daughters, whether they develop cancer per se. Each child has a 50 percent chance of one parent having the mutation.
If a person learns that they have inherited a harmful BRCA1 or BRCA2 mutation, that means they have a 50 percent chance that all of their siblings have both inherited the mutation.
What does a negative BRCA1 or BRCA2 test result mean?
A negative test result is easier to understand than positive results; because when ultimately depends on a person’s family history of cancer and whether a BRCA1 or BRCA2 mutation is detected in a blood relative.
If a close (first or second degree) relative of the person being tested is known to carry a harmful BRCA1 or BRCA2 mutation, a negative test result will result: this means that the person does not carry the harmful mutation responsible for the familial members of the cancer and thus cannot pass it on to their children. Such a test result is called a true negative. A person with such a test result is currently considered to have the same cancer risk as someone in the general population.
A negative result is less obvious if the person being tested has a family history of thought to be likely to have a harmful mutation in BRCA1 or BRCA2, although full gene testing indicates that the family does not have such a mutation. It’s highly unlikely that genetic testing might miss a known harmful BRCA1 or BRCA2 mutation, but it can happen. Moreover, scientists continue to discover new BRCA1 and BRCA2 mutations and have not identified potentially harmful ones. Therefore, it is possible that a person with a “negative” test result in this scenario has a harmful as yet unknown BRCA1 or BRCA2 mutation that has not yet been identified.
It is also possible for people to have a mutation in a gene other than BRCA1 or BRCA2 that increases the risk of cancer but cannot be detected by the test used. People considering genetic testing for BRCA1 and BRCA2 mutations may want to discuss these potential uncertainties with a genetic counselor prior to testing.
What does an uncertain or uncertain BRCA1 or BRCA2 test result mean?
Sometimes a genetic test finds a change in BRCA1 or BRCA2 that was not previously associated with cancer. This type of test result may be described as “uncertain” (often referred to as a “genetic variant of uncertain significance”) because it is not known whether this specific gene change affects a person’s risk of developing cancer. One study found that 10 percent of women who were tested for BRCA1 and BRCA2 mutations had such indeterminate results.
As more research is done and more people are tested for BRCA1 and BRCA2 mutations, scientists will learn more about these changes and cancer risk. Genetic counseling can help a person understand what an uncertain change in BRCA1 or BRCA2 could mean in terms of cancer risk. Over time, additional studies on variants of certain uncertainties may result in a specific mutation being reclassified as either deleterious or clearly not harmful.
How can a person with a positive test result correct their cancer risk?
Many options are available for managing cancer risk in people with known harmful BRCA1 or BRCA2 mutations. These include advanced screening, prophylactic (risk reduction) surgery and chemical prevention.
Enhanced Scan
Some women who test positive for BRCA1 and BRCA2 mutations may choose to start cancer screening at a younger age than the general population, or to be screened more often. For example, some experts recommend that women who carry a harmful BRCA1 or BRCA2 mutation undergo clinical breast exams starting at age 25 to 35 (19). Some expert groups recommend that women who carry such a mutation should have a mammogram every year between the ages of 25 and 35.
Advanced screening can increase the chances of finding breast cancer at an earlier stage, where the chances of successful treatment may be earlier. Women who have a positive test result should ask their medical professionals about the possible harms of diagnostic tests that cause radiation (mammograms or x-rays).
Recent research has shown that MRI (Emar) may be more sensitive than mammography for women at high risk of breast cancer. However, mammography can also identify some breast cancers that are not identified by MRI, and Emar can be more specific (i.e. lead to more false positive results) than mammography. Some organizations, such as the American Cancer Society and the National Comprehensive Cancer Network, recommend annual mammography and MRI screening for women at high risk of breast cancer.
There is currently no effective ovarian cancer screening method available. Some groups recommend transvaginal ultrasound, CA-125 blood testing, and clinical examination for ovarian cancer screening in women with deleterious BRCA1 or BRCA2 mutations, but none of these methods detect ovarian tumors at an early enough stage to reduce the risk. For an effective screening method to be considered effective, the death toll from ovarian cancer must have reduced the death rate from the disease in question. This standard has not yet been caught for ovarian cancer screening.
The benefits of screening for breast and other cancers that carry deleterious mutations in BRCA1 or BRCA2 are also unknown, but some expert groups recommend that men who are known to have a harmful mutation get regular mammograms as well as prostate cancer testing. The value of these screening strategies remains unproven.
Prophylactic (Risk Reduction) Surgery
Prophylactic surgery is to remove as much “at risk” tissue as possible. Women may choose to have both breasts removed (bilateral prophylactic mastectomy) to reduce their risk of breast cancer. Surgery to remove a woman’s ovaries and fallopian tubes (bilateral prophylactic salpingo-oophorectomy) can reduce her risk of ovarian cancer. Removing the ovaries reduces the risk of breast cancer in premenopausal women by removing a source of hormones that accelerate the growth of some types of breast cancer.
There is no evidence for the effectiveness of dual prophylactic mastectomy in reducing breast cancer risk in men with bilateral deleterious BRCA1 or BRCA2 mutations or with a history of breast cancer. For this reason, bilateral prophylactic mastectomy for men at high risk of breast cancer is considered an experimental procedure and insurance companies do not normally cover it.
Prophylactic surgery does not fully guarantee that cancer will not develop, because not all at-risk tissue can be removed with these procedures. Some women have developed breast cancer, ovarian cancer, or primary peritoneal carcinomatosis (a type of cancer similar to ovarian cancer) even after prophylactic surgery. Still, the reduction in mortality associated with this surgery is significant: Studies show that women who underwent bilateral prophylactic salpingo-oophorectomy had an 80% reduction in the risk of dying from ovarian cancer, a 56% reduction in the risk of dying from breast cancer) and dying from any cause. 77 decreases are observed.
Emerging evidence suggests that, unlike previous studies, the fact that removing the ovaries and fallopian tubes protects against the development of breast cancer and ovarian cancer may be similar for carriers of BRCA1 and BRCA2 mutations.
What are some of the benefits of genetic testing for breast and ovarian cancer risk?
Regardless of whether a person gets a positive or negative result, genetic testing can have benefits.
The potential benefits of a true negative result include learning that there is a sense of relief about future cancer risk, that one’s child is not at risk of perceiving the family’s cancer susceptibility, and that there may be no special examination, testing, or preventive surgery. necessary.
A positive test result can be alleviated by resolving uncertainties about future cancer risk and allow people to make informed decisions about their future, including taking steps to reduce cancer risk. In addition, people with a positive test result may choose to participate in medical research that may, in the long run, help reduce deaths from hereditary breast and ovarian cancer.
What are some of the possible harms of genetic testing for breast and ovarian cancer risk?
The direct medical harm of genetic testing is minor, but knowing the test results can have detrimental effects on a person’s emotions, social relationships, finances, and medical choices.
People who get a positive test result may feel anxious, depressed, or angry. They may have difficulty choosing whether to have conservative surgery or which surgery to have.
People who get a negative test result may experience “survivor guilt”, possibly because of the knowledge that they are not at risk of developing a disease that affects one or more loved ones.
Because genetic testing reveals information about multiple family members, the emotions caused by the test results can create tension between families. Test results can also affect personal life choices, such as career, marriage, and fertility decisions.
Violation of privacy and confidentiality of genetic test results are additional potential risks. However, general health insurance and health insurance and various laws protect the confidentiality of a person’s genetic information. Moreover, although privacy law, along with many state laws, does not cover life insurance, disability insurance or long-term care insurance, our laws prohibit discrimination based on genetic information in relation to social security insurance and employment.
Finally, there is a small chance that you may encounter misleading results from labs run by non-medical people, which we refer to as under the counter, where test results may not be accurate, making people make decisions based on misinformation. While there are often no false results, people with these concerns should address their concerns at the time of application. We remind you that centers that are not owned by doctors cannot be trusted.
What are the implications of inheriting a harmful BRCA1 or BRCA2 mutation for breast and ovarian cancer prognosis and treatment?
A number of studies have investigated possible clinical differences between harmful BRCA1 or BRCA2 mutations not associated with these mutations and breast cancer and ovarian cancer associated with cancers.
In the long term, there is some evidence that women carrying these mutations are more likely to develop a second cancer in the same (ipsilateral) breast or opposite (contralateral) breast compared to women without this mutation. Therefore, some women with a harmful BRCA1 or BRCA2 mutation who develop breast cancer in one breast choose to have a bilateral mastectomy, even if they are otherwise candidates for breast-conserving surgery. In fact, because of an increased risk of a second breast cancer among carriers of the BRCA1 and BRCA2 mutations, some doctors believe that women with early-onset breast cancer and a family history of a mutation in one of these genes are diagnosed with breast cancer.
Breast cancer in women with deleterious BRCA1 mutations is more likely to be “triple negative cancers” (eg, breast cancer cells lack estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein), and these are often “triple negative cancers” than other breast cancers. worse prognosis.
Because the products of the BRCA1 and BRCA2 genes are involved in DNA repair, some researchers have suggested that cancer cells with a harmful mutation in any of these genes may be more susceptible to DNA-damaging anticancer agents. In preclinical studies, drugs called PARP inhibitors, which block the repair of DNA damage, have been found to stop the growth of cancer cells with BRCA1 or BRCA2 mutations. These drugs also showed some activity in cancer patients carrying BRCA1 or BRCA2 mutations, and researchers continue to develop and test these drugs.
What research is currently being done to help individuals with harmful BRCA1 or BRCA2 mutations?
Research studies are underway to find new and better ways to detect, treat and prevent cancer in people with mutations in BRCA1 and BRCA2. Additional studies have focused on improving genetic counseling methods and outcomes. Our knowledge in these areas is developing rapidly.
Do inherited mutations in other genes increase the risk of breast and/or tumor ovarian tumors?
Yes. While deleterious mutations in BRCA1 and BRCA2 are responsible for the disease in about half of families with multiple cases of breast cancer and in 90 percent of families with both breast and ovarian cancer, mutations in a number of other genes have been associated with increased risks of breast cancer and/or ovarian cancer. These other genes include several factors associated with hereditary Cowden syndrome, Peutz-Jeghers syndrome, Li-Fraumeni syndrome, and Fanconi anemia that increase the risk of many types of cancer.
Mutations in many of these other genes are associated with smaller increases in breast cancer risk than are seen with BRCA1 and BRCA2 mutations. However, researchers recently reported that inherited mutations in the PALB2 gene associated with inherited BRCA1 and BRCA2 mutations are nearly identical to breast cancer risk. They estimated that 33 percent of women who inherit a harmful mutation in PALB2 will develop breast cancer by age 70. The risk of breast cancer associated with a harmful PALB2 mutation is even higher for women with a family history of breast cancer: 58 percent of these women will develop breast cancer by age 70.
PALB2 is a tumor suppressor gene like BRCA1 and BRCA2. The PALB2 gene produces a protein that interacts with the proteins produced by the BRCA1 and BRCA2 genes to help repair breaks in DNA. Harmful mutations in PALB2 (also known as FANCN) are associated with an increased risk of ovarian, pancreatic, and prostate cancers, in addition to an increased risk of breast cancer. Mutations in PALB2 can cause FA-N, a Fanconi anemia subtype associated with childhood solid tumors when inherited from each parent.
Although genetic testing for PALB2 mutations is available, expert groups have not yet developed definitive guidelines for who to test in individuals with PALB2 mutations or for the management of breast cancer risk.