BRCA1

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Breast cancer 1 gene (BRCA1) is at 17q21.

Mutations cause hereditary breast-ovarian cancer syndrome. This susceptibility can be accurately modeled[1]

Gene product functions as a transcriptional coactivator, with DNA binding properties and associates with the Fanconi anemia nuclear complex essential for protection against chromosome breakage. It thus has a role in DNA repair.

Treatment

Prophylactic bilateral total mastectomy or oophorectomy in carriers of BRCA1 mutations can decrease the risk of cancer, particularly breast cancer. The discovery in 2016 that denosumab, a drug already used to prevent osteoporosis, inhibits RANKL signaling in pre-neoplastic BRCA1 mutant breast tissue reducing progesterone-induced proliferation is likely to rapidly lead to preventive clinical trials as current prevention strategies include these prophylactic operations[2].

In ovarian cancer BRCA1 mutation carriers have a tendency to more aggressive disease than BRCA2 mutation carriers[3] .

Patients with prostate cancer with BRCA1 mutations tend to have more aggressive disease[4].

External link

Boardicea model of BRCA2/BRCA1 risk of breast cancer in women

References

  1. Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC, Olsson H, Johannsson O, Borg A, Passini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tryggvadottir L, Syrjakoski K, Kallioniemi OP, Eerola H, Nevanlinna H, Pharoah PD, Easton DF. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. British journal of cancer. 2008 Apr 22; 98(8):1457-66.(Link to article – subscription may be required.)
  2. Nolan E, Vaillant F, Branstetter D, Pal B, Giner G, Whitehead L, Lok SW, Mann GB, Rohrbach K, Huang LY, Soriano R, Smyth GK, Dougall WC, Visvader JE, Lindeman GJ. RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. Nature medicine. 2016 Jun 20.(Epub ahead of print) (Link to article – subscription may be required.)
  3. Byrd LM, Shenton A, Maher ER, Woodward E, Belk R, Lim C, Lalloo F, Howell A, Jayson GC, Evans GD. Better Life Expectancy in Women with BRCA2 Compared with BRCA1 Mutations Is Attributable to Lower Frequency and Later Onset of Ovarian Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2008 Jun; 17(6):1535-42.(Link to article – subscription may be required.)
  4. Mitra A, Fisher C, Foster CS, Jameson C, Barbachanno Y, Bartlett J, Bancroft E, Doherty R, Kote-Jarai Z, Peock S, Easton D, Eeles R. Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype. British journal of cancer. 2008 Jan 29; 98(2):502-7.(Link to article – subscription may be required.)