brca mutation 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. 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. 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. brca mutationabsolute risk of cancers in brca1 or brca2 mutation.specialtymedical genetics 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. however, brca mutations can increase the risk of other cancers, such as colon cancer, pancreatic cancer, and prostate cancer. methods to diagnose the likelihood of a patient with mutations in brca1 and brca2 getting cancer were covered by patents owned or controlled by myriad genetics. myriad's business model of exclusively offering the diagnostic test led to myriad growing from being a startup in 1994 to being a publicly traded company with 1200 employees and about $500m in annual revenue in 2012; it also led to controversy over high prices and the inability to get second opinions from other diagnostic labs, which in turn led to the landmark association for molecular pathology v. myriad genetics lawsuit. biallelic and homozygous inheritance of a brca gene leads to a severe form of fanconi anemia, and is embryonically lethal in the majority of the cases. health effects further information: brca1 and brca2 women with deleterious mutations in either the brca1 or brca2 genes have a high risk of developing breast and/or ovarian cancer. because different studies look at different populations, and because different types of mutations have somewhat different risks, the risk is best expressed as a range, rather than a single number.: 89–111 approximately 50% to 65% of women born with a deleterious mutation in brca1 will develop breast cancer by age 70, and 35% to 46% will develop ovarian cancer by age 70. approximately 40% to 57% of women with a deleterious mutation in brca2 will develop breast cancer by age 70, and 13% to 23% will develop ovarian cancer by age 70.: 89–111 women with a breast cancer associated with a brca mutation have up to a 40% probability of developing a new primary breast cancer within 10 years following initial diagnosis if they did not receive tamoxifen treatment or have an oophorectomy. the woman's ten-year risk for ovarian cancer is also increased by 6-12% under these conditions. statistics for brca-related ovarian cancer typically encompass not only cancer of the ovaries themselves, but also peritoneal cancer and the very rare, but somewhat easier to detect, cancer of the fallopian tubes. women with a brca mutation have more than 100 times the normal rate of fallopian tube cancer.: 275–302 these three types of these cancers can be difficult to distinguish in their advanced stages. cancer onset brca-related breast cancer appears at an earlier age than sporadic breast cancer.: 89–111 it has been asserted that brca-related breast cancer is more aggressive than normal breast cancer, however most studies in specific populations suggest little or no difference in survival rates despite seemingly worse prognostic factors. brca1 is associated with triple-negative breast cancer, which does not respond to hormonal treatments and cannot be usefully treated with some drugs, such as trastuzumab. breast cancer often appears about two decades earlier than normal.: 89–111 brca2 is associated primarily with post-menopausal breast cancer, although the risk of pre-menopausal breast cancer is significant. it is typically highly responsive to hormonal treatments.: 89–111 brca-related ovarian and fallopian tube cancer is more treatable than average because it is unusually susceptible to platinum-based chemotherapy like cisplatin.: 275–302 brca1-related ovarian cancer appears at younger ages, but the risk for women with brca2 climbs markedly at or shortly after menopause.: 275–302 survival impact among women who die before age 70...72 / 10046 / 10011 / 10072% of women with a brca1 mutation and 46% of women with a brca2 mutation (and no screening or medical interventions) who die before age 70 will die from breast or ovarian cancer. 11% of women in the us who die before age 70 will die from breast or ovarian cancer. likelihood of a 25-year-old woman surviving to age 70 (without screening or medical interventions to prevent cancer) group percentage surviving to age 70 brca1 mutation 59 brca2 mutation 71 typical woman 84 a 25-year-old woman with no mutation in her brca genes has an 84% probability to reach at least the age of 70. of those not surviving, 11% die from either breast or ovarian cancer, and 89% from other causes. compared to that, a woman with a high-risk brca1 mutation, if she had breast cancer screening but no prophylactic medical or surgical intervention, would have only 59% chance to reach age 70, twenty-five percentage points lower than normal. of those women not surviving, 26% would die of breast cancer, 46% ovarian cancer, and 28% other causes. women with high-risk brca2 mutations, with screening but with no prophylactic medical or surgical intervention, would have only 71% chance to reach age 70, thirteen percentage points lower than normal. of those not surviving, 21% would die of breast cancer, 25% ovarian cancer and 54% other causes. the likelihood of surviving to at least age 70 can be improved by several medical interventions, notably prophylactic mastectomy and oophorectomy. male breast cancer 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.: 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.: 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.: 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.: ch8 other cancers mutations have been associated with increased risk of developing any kind of invasive cancer, including stomach cancer, pancreatic cancer, prostate cancer, and colon cancer. 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.: 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.: 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.: ch8 cancer of the pancreas tends to run in families, even among brca families.: 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. 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. asymptomatic screening is invasive and may be recommended only to brca2 carriers who also have a family history of pancreatic cancer.: 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.: ch8 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.: 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.: 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. mutations of brca2 are also found in many t-cell lymphomas and chronic lymphocytic leukemias. childbearing the dilemma of whether or not to have children may be a source of stress for women who learn of their brca mutations during their childbearing years. there is likely little or no effect of a brca gene mutation on overall fertility, although women with a brca mutation may be more likely to