Editing BRCA2 (section)

== Clinical significance ==
[[File:BRCA1 and BRCA2 mutations and absolute cancer risk.jpg|thumb|310px|Absolute risk of cancers in [[BRCA1]] or BRCA2 mutation.<ref name="Petrucelli_2016">{{cite book | vauthors = Petrucelli N, Daly MB, Pal T | veditors = Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Mirzaa G, Amemiya A | chapter = BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer | title = GeneReviews | publisher = University of Washington, Seattle | orig-date = September 1998 | date = December 2016 | pmid = 20301425 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK1247/ }}</ref>]]
{{Further|BRCA mutation}}
Certain variations of the ''BRCA2'' gene increase risks for [[breast cancer]] as part of a [[hereditary breast–ovarian cancer syndrome]]. Researchers have identified hundreds of mutations in the ''BRCA2'' gene, many of which cause an increased risk of cancer. ''BRCA2'' mutations are usually insertions or deletions of a small number of DNA base pairs in the gene. As a result of these mutations, the protein product of the ''BRCA2'' gene is abnormal, and does not function properly. Researchers believe that the defective ''BRCA2'' protein is unable to fix DNA damage that occurs throughout the genome.  As a result, there is an increase in mutations due to error-prone [[DNA repair#Translesion synthesis|translesion synthesis]] past un-repaired DNA damage, and some of these mutations can cause cells to divide in an uncontrolled way and form a tumor.

People who have two mutated copies of the ''BRCA2'' gene have one type of [[Fanconi anemia]]. This condition is caused by extremely reduced levels of the BRCA2 protein in cells, which allows the accumulation of damaged DNA. Patients with Fanconi anemia are prone to several types of [[leukemia]] (a type of blood cell cancer); solid tumors, particularly of the head, neck, skin, and reproductive organs; and [[bone marrow suppression]] (reduced blood cell production that leads to [[anemia]]).  Women having inherited a defective ''BRCA1'' or ''BRCA2'' gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have [[prophylactic surgery]]. There has been much conjecture to explain such apparently striking tissue specificity. Major determinants of where ''BRCA1''- and ''BRCA2''-associated hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation, or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to carcinogens and an infectious process. An innate genomic deficit impairs normal responses and exacerbates the susceptibility to disease in organ targets. This theory also fits data for several tumor suppressors beyond ''BRCA1'' or ''BRCA2''. A major advantage of this model is that it suggests there are some options in addition to prophylactic surgery.<ref name="Levin2012">{{cite journal | vauthors = Levin B, Lech D, Friedenson B | title = Evidence that BRCA1- or BRCA2-associated cancers are not inevitable |journal=Molecular Medicine | volume = 18 | issue = 9 | pages = 1327–37 | year = 2012 | pmid = 22972572 | pmc = 3521784 | doi = 10.2119/molmed.2012.00280 }}</ref>

In addition to breast cancer in men and women, mutations in ''BRCA2'' also lead to an increased risk of [[ovarian cancer|ovarian]], [[Fallopian tube|uterine tube]], [[prostate cancer|prostate]] and [[pancreatic cancer]]. In some studies, mutations in the central part of the gene have been associated with a higher risk of [[ovarian cancer]] and a lower risk of [[prostate cancer]] than mutations in other parts of the gene. Several other types of cancer{{which|date=July 2024}} have also been seen in certain families with ''BRCA2'' mutations.{{cn|date=July 2024}}

In general, strongly inherited gene mutations (including mutations in ''BRCA2'') account for only 5-10% of breast cancer cases; the specific risk of getting breast or other cancer for anyone carrying a ''BRCA2'' mutation depends on many factors.<ref>{{cite web | url = http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional/page2| title = High-Penetrance Breast and/or Ovarian Cancer Susceptibility Genes | publisher=National Cancer Institute | access-date = 7 December 2012}}</ref>