.. ient pamphlet) When BRCA1 or BRCA2 mutation is inherited it is considered a dominant factor. People receive one BRCA1 allele from their mom and one BRCA1 allele from their dad. The same goes for any other gene pairs. BRCA1 is not just inherited by women, but men as well. It is NOT a sex-linked trait.
In order to study how organisms inherit genes, health care professionals use a Punnet square in order to understand how people inherit a gene. Finding out if a person does have a BRCA1 or BRCA2 mutation is another process. (Myriad Genetic Pamphlet) DIAGRAM 5 Inherited alleles of family tumor suppressor gene predispose individuals to particular types of cancer; this is one of the reasons why cancer occurs. Doctors are still not sure what causes BRCA1 and BRCA2 genes to mutate. In addition to trying to find mutations on the BRCA1 and BRCA2 genes, doctors are telling people to stay healthy in order to decrease a persons risk of cancer. Some mutations not on BRCA1 and BRCA2 stop the gene from functioning, while others force genes to create abbreviated or misshapen molecules (proteins) that function incorrectly. (Travis 374) The risk of harboring a mutation is not limited to women who have a family history of breast or ovarian cancer.
Results of this represent a minimal estimate of the frequency of BRCA1 mutations. Right now scientists have found over 100 distinct germ-line mutations of BRCA1 that have been identified in more than 100 patients with breast/ovarian cancer. A recent collaborative survey describing 80 germ-line mutations summarizes the spectrum and frequency of BRCA1 mutations identified to date primary in the high-risk families. (Langston 3) No somatic mutations of the BRCA1 or BRCA2 genes have been identified in sporadic breast cancers, though 5 mutations have been found in sporadic ovarian tumors. This suggest that BRCA1 is primarily a germ-line mutation.
(Gaithersburg 1) The outcome of BRCA1 mutations may reflect the different duties the genes protein performs in breast and ovarian cells. Scientists think that there are only 3 main types of mutations on BRCA1. Additional mutations have been found twice by a complete screening of the cDNA. The total percent of a recurring mutations is 31%. (Davison www.cancer.org) Inherited mutations on BRCA1 and BRCA2 are known to contribute to a predisposition to breast cancer. Heterozygotes for mutations in the ataxia-telangiectasia gene also increases a womans risk for breast cancer.
Females who are obligated carriers of ataxia telangiectasia have a 4 to 12 times increased relative risk of developing breast cancer as compared to the general female population. Increasing their overall chances of developing breast cancer. (Anderson 408) Mutations in the BRCA1 gene are identified through a highly technical process; the sequencing of DNA obtained from a blood sample. Currently Myriad Genetic Laboratories is testing individuals under clinical research protocols with institutional review board approval. The decision to be tested must be made by the individual, in consultation with a healthcare professional. Those who may benefit form the BRCA1 genetic susceptibility testing include: (American Can Soc 13) ~women who have been diagnosed with breast cancer, especially those with early onset-disease. ~women who have been diagnosed with ovarian cancer. ~women with a family history of either breast or ovarian cancer.
~women who are blood relatives of those who carry a BRCA1 mutation. ~men who are blood relatives of those who carry a BRCA1 mutation. If the family history of a woman with breast/ovarian cancer is uncertain or unknown, testing may still be appropriate. For example, she may have few female relatives or, since men also have a 50% chance of passing the mutation to each of their offspring, the susceptibility may have been passed through her paternal line. These and other factors need to be considered in the womans decision to be tested. (Ovarian Cancer Pamphlet) Early cancer detection provides the best opportunity for reducing mortality for all women. Women who test positive for BRCA1 genetic susceptibility may benefit from increased surveillance.
Some healthcare professionals are prescribing earlier implementation and more frequent utilization of the following surveillance methods: (Ovarian Cancer Pamphlet) Breast cancer detection guidelines: ~breast self-exams. ~clinical breast exams. ~mammograms. ~consultation with a qualified healthcare professional if a change in breast tissue is detected. Ovarian cancer guidelines: ~CA-125 serum tumor marker testing ~transvaginal ultrasound ~rectovaginal pelvic examination Women who have a BRCA1 mutation and have been diagnosed with breast cancer are at an increased risk of developing cancer in the other breast.
This may affect treatment decisions, i.e., the choice between a mastectomy or a lumpectomy of the affected breast, and either prophylactic mastectomy of the unaffected breast and/or prophylactic oophorectomy. (Doctor Pamphlet on breast cancer/Gaitherburg) Ways to treat breast cancer: ~Prophylactic oophorectomy. Many clinicians believe that this is the treatment of choice for the women who carry BRCA1 mutation or for those who have a strong family history of breast cancer. A bilateral removal of the ovaries to decrease estrogen production is effective as well. Other considerations include the individuals risk for cardiovascular disease and osteoporosis and her concerns about sterility.
(Doctors Pamphlet on BRCA1 and 2) ~Prophylactic mastectomy. Because dense breast tissue may interfere with the clinical examination and mammography, and in premenopausal women every breast cell has a mutated gene placing a woman at a 95% risk during her lifetime for breast cancer, the volume of the breast tissue that can be affected is reduced through mastectomy, making prophylactic surgery appropriate for women who carry a BRCA1 mutation. However, because surgery cannot remove all breast tissue, the risk of developing breast cancer cannot be totally eliminated. (Doctors Pamphlet on BRCA1 and 2) Another kind of treatment is hormone replacement therapy. Hormone replacement therapy has been shown to be effective in relieving some of the conditions often associated with menopause, as well as decreasing the risk of a heart attack and osteoporosis. However, the use of replacement hormones may increase the risk of breast and endometrial cancer. Post menopausal women who are currently taking hormones (estrogen or a combination of estrogen and progesterone) have a relative risk of 1.46% of developing breast cancer compared to post-menopausal women who have never taken hormones or had breast cancer.
The effect of hormone replacement therapy for shorter periods of time and for women who carry a mutated BRCA1 gene is currently unknown. (Gayther 1462) There are some life modifications that women can make in order to decrease their chance of breast cancer. Women who carry a BRCA1 mutation should be encouraged to evaluate their current lifestyle habits and, if necessary and/or appropriate, modify the following: (Gross 88) Age at first pregnancy: Data indicates that women who deliver their first child before age 30 are less likely to develop breast and ovarian cancer. Body weight: individuals who are 40% or more over- weight may have an increased risk of breast and ovarian cancer. In addition, maintaining desirable body weight increases efficacy of cancer screening procedures. Exercise: Physical activity during a womans reproductive years affect the production of estrogen and other sex hormones.
This may provide a protective effect against breast cancer risk. Tobacco use: A study indicates that a womans risk of dying from breast cancer increases 25% if the women smokes cigarettes. Diet: Some studies suggest that eating a balanced diet has an anti-tumor affect. Recommendations for a balanced diet include foods low in fat and rich in fiber and antioxidants; green leafy vegetables; soy products; and broccoli, cabbage, brussel sprouts, and other cruciferous vegetables. Alcohol: Some studies indicate there is some link between alcohol consumption and the development of breast cancer, although no causal relationship has not been proven. (Gross 89) SEE DIAGRAM 6 In the future, scientists hope discoveries will lead to gene therapy, but for now there is little one can do about a genetic predisposition beyond counseling and lifestyle changes.
The BRCA1/BRCA2 genetic susceptibility test is commercially available through Myriad Genetic and OncorMed Laboratories. Testing to verify sensitivity, specificity, and other parameters will commence at cancer centers throughout the U.S. Educational materials will be provided to healthcare professionals who offer BRCA1/BRCA2 testing to assist in presenting and discussing issues with patients both before and after the test. (Breast/Ovarian Pamphlet) Having a test for either BRCA1 or BRCA2 could affect a persons ability to get or to keep insurance in the future. If a mutation is found in someones family that increases the risk for developing cancer, it could affect their familys ability to get or to keep insurance (health, life, and disability). One may experience loss of insurance, inability to qualify for new insurance, increased premium payments, or decreased coverage.
A person may be locked into a job to keep coverage, or lose coverage in the event of a job loss. (Hereditary Breast Cancer 4) Patients should talk to their doctor about how the information will be kept in their medical record. People who are concerned about how their test results will be used need to consider paying for tests out of their own pockets. Legislators are in the process of introducing state bills which ban such discrimination from employers and insurance companies. Twenty states already have statutes that, to varying degrees, protect the confidentiality of genetic test results and protect them from employment or insurance discrimination. The presence of a mutation in BRCA1 or BRCA2 indicates that there is a risk to develop cancer.
It does not mean that cancer will definitely develop. Although testing is very accurate, there is a chance that an inherited mutation in BRCA1 or BRCA2 will not be detected or that a mutation exists in another gene for which testing was not done. Cancer can and does occur for other reasons.. (Hereditary Breast Cancer 4) There are psychological risks for being tested. Some people may also have difficulty in knowing that they carry a gene which increases their risk to develop breast cancer. They may experience emotions, such as: anger, denial, anxiety, or shock; fear of cancer or of the future; worry about their health, family, employability; changed self-image; guilt for possibly passing the gene to children; worry about the future medical costs and insurability.
These are all normal reactions. (Hereditary Breast Cancer 4) If a mutation in BRCA1 and BRCA1 is found, one will be encouraged to inform other family members who may also carry the mutation. In the process, other family members may also find out confidential information. For example, someone may disclose that a family member is adopted. Therefore, sometimes relationships in families may be affected. (Hereditary Breast Cancer 4) In conclusion, it is believed that 1 out of 3 women will inherit breast cancer during their life time, though others may disagree.
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