BRCA2 Mutation Panel
BRCA Gene Overview:
BReast CAncer gene (BRCA1 and BRCA2) are human genes that produce tumor suppressor proteins and help repair damaged DNA, thereby playing a role in ensuring the stability of each cell’s genetic material. if there is any mutation or alteration in the genes, the synthesis of proteins as well as its functioning will get affected, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.
Women who carry the inherited mutations in these genes are at an increased risk of developing breast cancer and ovarian cancer compared with the general population. Specific inherited mutations in BRCA1 and BRCA2 most notably increase the risk of female breast and ovarian cancers, but they have also been associated with increased risks of several additional types of cancer.
People who have inherited mutations in BRCA1 and BRCA2 tend to develop breast and ovarian cancers at younger ages than people who do not have these mutations. The BRCA genetic test is offered to the people who are likely to have an inherited mutation based on personal or family history, or who have a specific type of breast cancer. The BRCA gene test is routinely performed on women at average risk of breast and ovarian cancers.
People who are advised for genetic testing can approach for genetic counselling, which helps them to understand the possible cancer risk and the benefits of undertaking genetic test.
BRCA2 Mutation and Breast Cancer risk:
BReast CAncer gene (BRCA1 and BRCA2) are human genes that produce tumor suppressor proteins and help repair damaged DNA, thereby playing a role in ensuring the stability of each cell’s genetic material. if there is any mutation or alteration in the genes, the synthesis of proteins as well as its functioning will get affected, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.
Women who carry the inherited mutations in these genes are at an increased risk of developing breast cancer and ovarian cancer compared with the general population. Specific inherited mutations in BRCA1 and BRCA2 most notably increase the risk of female breast and ovarian cancers, but they have also been associated with increased risks of several additional types of cancer.
People who have inherited mutations in BRCA1 and BRCA2 tend to develop breast and ovarian cancers at younger ages than people who do not have these mutations. The BRCA genetic test is offered to the people who are likely to have an inherited mutation based on personal or family history, or who have a specific type of breast cancer. The BRCA gene test is routinely performed on women at average risk of breast and ovarian cancers.
People who are advised for genetic testing can approach for genetic counselling, which helps them to understand the possible cancer risk and the benefits of undertaking genetic test.
BRCA2 Mutation and Breast Cancer risk:
- BRCA germline mutations contribute significantly to the development of familial/hereditary breast and ovarian cancer.
- These mutations are distributed uniformly along the entire coding region and intronic sequences flanking each exon.
- About 69% of women who inherit a harmful BRCA2 mutation will develop breast cancer by the age of 80 (1)
- Like women from the general population, those with harmful BRCA1 or BRCA2 mutations also have a high risk of developing a new primary cancer in the opposite (contralateral) breast in the years following a breast cancer diagnosis.
- It has been estimated that, by 20 years after a first breast cancer diagnosis, 26% of women who inherit a harmful BRCA2 mutation will develop cancer in their other breast (1).
- Certain mutations in BRCA2, if they are inherited from both parents, can cause a rare form of Fanconi anemia, a syndrome that is associated with childhood solid tumors and development of acute myeloid leukemia (2; 3).
- Truncating mutations and missense mutations in the BRCA2 gene are found in a large number of familial breast cancer cases.
- In addition, for sporadic breast cancer, a reduction in the expression of BRCA rather than the presence of mutations has been observed.
- The lack of a functional BRCA leads to impaired repair of DNA double strand breaks, cell cycle progression and transcriptional regulation, thereby causing the development of neoplasms.
- Harmful mutations in BRCA1 and BRCA2 increase the risk of several cancers in addition to breast and ovarian cancer.
- These include fallopian tube cancer (4; 5) and peritoneal cancer (6).
- Men with BRCA2 mutations, and to a lesser extent BRCA1 mutations, are also at increased risk of breast cancer (7) and prostate cancer (8).
- If they are inherited from both parents, can cause a rare form of Fanconi anemia, a syndrome that is associated with childhood solid tumors and development of acute myeloid leukemia (2; 3).
- Likewise, certain mutations in BRCA1 (also known as FANCS), if they are inherited from both parents, can cause another Fanconi anemia subtype (9).
- Genetic counseling is generally recommended before and after any genetic test for an inherited cancer syndrome.
- A hereditary cancer risk assessment based on an individual’s personal and family medical history.
- When an individual’s family history mentions the presence of the BRCA1 and BRCA2 mutation, it is recommended first to test the family member who has cancer.
- If the cancer patient in the family is reported to have a BRCA1 or BRCA2 mutation, then other family members are advised to consider genetic test and genetic counseling, so that, they can learn more about the potential cancer risks.
- If a woman with an unknown family history has an early-onset breast cancer or a man with an unknown family history is diagnosed with breast cancer, that individual may want to consider genetic counseling and testing for a BRCA1 or BRCA2 mutation.
- A history of breast cancer at a young age in two or more close relatives, such as your parents, siblings or children are also recommended.
- Breast cancer diagnosed before age 50 years
- A personal history of triple negative breast cancer diagnosed at age 60 or younger
- Cancer in both breasts of the same woman
- Both breast and ovarian cancers in either the same woman or the same family
- Multiple breast cancers in the family
- Two or more primary types of BRCA1- or BRCA2-related cancers in a single family member
- A personal history of both breast and ovarian cancers
- A relative with a known BRCA1 or BRCA2 mutation
- Kuchenbaecker KB, Hopper JL, Barnes DR, et al. JAMA 2017; 317(23):2402-2416.
- Howlett NG, Taniguchi T, Olson S, et al. Science 2002; 297(5581):606-609.
- Alter BP. Best practice & research. Clinical Haematology 2014; 27(3-4):214-21.
- Brose MS, Rebbeck TR, Calzone KA, et al. Journal of the National Cancer Institute 2002; 94(18):1365–1372.
- Finch A, Beiner M, Lubinski J, et al. JAMA 2006; 296(2):185–192.
- Levine DA, Argenta PA, Yee CJ, et al. Journal of Clinical Oncology 2003; 21(22):4222–4227.
- Tai YC, Domchek S, Parmigiani G, Chen S. Journal of the National Cancer Institute 2007; 99(23):1811–1814.
- Levy-Lahad E, Friedman E. British Journal of Cancer 2007; 96(1):11–15.
- Sawyer SL, Tian L, Kähkönen M, et al. Cancer Discovery 2015; 5(2):135-142.