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A ''BRCA'' mutation is a mutation in either of the ''BRCA1'' and ''BRCA2'' genes, which are tumor 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.〔(【引用サイトリンク】 url = http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA )〕 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. 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.〔(US5747282 )〕〔(US5837492 )〕 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;〔(Myriad Investor Page—see "Myriad at a glance" ) accessed October 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. ==Genes and mutations== Both ''BRCA'' genes are tumor suppressor genes that produce proteins that are used by the cell in an enzymatic pathway that makes very precise, perfectly matched repairs to DNA molecules that have double-stranded breaks.〔 The pathway requires proteins produced by several other genes, including ''CHK2'', ''FANCD2'' and ''ATM''.〔 Harmful mutations in any of these genes disable the gene or the protein that it produces. The cancer risk caused by ''BRCA1'' and ''BRCA2'' mutations are inherited in a dominant fashion even though usually only one mutated allele is directly inherited. This is because people with the mutation are likely to acquire a second mutation, leading to dominant expression of the cancer. A mutated ''BRCA'' gene can be inherited from either parent. Because they are inherited from the parents, they are classified as ''hereditary'' or ''germline mutations'' rather than ''acquired'' or ''somatic mutations''. Cancer caused by a mutated gene inherited from an individual's parents is a ''hereditary cancer'' rather than a ''sporadic cancer''. Because humans have a diploid genome, each cell has two copies of the gene (one from each biological parent). Typically only one copy contains a disabling, inherited mutation, so the affected person is heterozygous for the mutation. If the functional copy is harmed, however, then the cell is forced to use alternate DNA repair mechanisms, which are more error-prone. The loss of the functional copy is called ''loss of heterozygosity'' (LOH). Any resulting errors in DNA repair may result in cell death or a cancerous transformation of the cell.〔 There are many variations in ''BRCA'' genes, and not all changes confer the same risks. Some variants are harmless; others are known to be very harmful. Some single nucleotide polymorphisms may confer only a small risk, or may only confer risk in the presence of other mutations or under certain circumstances. In other cases, whether the variant is harmful is unknown. Variants are classified as follows:〔 * Deleterious mutation: The change is proven to cause significant risks. Often, these are frameshift mutations that prevent the cell from producing more than the first part of the necessary protein. * Suspected deleterious: While nothing is proven, the variation is currently believed to be harmful. * Variant of unknown significance (VUS): Whether the change has any effect is unknown. This is a common test result, and most variations began in this category. As more evidence is acquired, these are re-classified. * Variant, favor polymorphism: While nothing is proven, the variation is currently believed to be harmless. * Benign polymorphism: The change is classified as harmless. These may be reported as "no mutation". Deleterious mutations have high, but not complete, genetic penetrance, which means that people with the mutation have a high risk of developing disease as a result, but that some people will not develop cancer despite carrying a harmful mutation. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「BRCA mutation」の詳細全文を読む スポンサード リンク
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