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BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population.

Nielsen, Henriette Roed; Nilbert, Mef; Petersen, Janne; Ladelund, Steen; Thomassen, Mads; Pedersen, Inge Søkilde; Hansen, Thomas V O; Skytte, Anne-Bine; Borg, Åke LU and Therkildsen, Christina (2016) In Familial Cancer
Abstract
Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8... (More)
Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer. (Less)
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author
organization
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type
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publication status
published
subject
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Familial Cancer
publisher
Kluwer
external identifiers
  • pmid:26833046
  • scopus:84985881469
  • wos:000382681500002
ISSN
1389-9600
DOI
10.1007/s10689-016-9875-7
language
English
LU publication?
yes
id
417d6689-3e18-4e34-a2e0-a73d56f7d92e (old id 8829983)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26833046?dopt=Abstract
date added to LUP
2016-03-01 12:36:16
date last changed
2017-11-05 04:43:24
@article{417d6689-3e18-4e34-a2e0-a73d56f7d92e,
  abstract     = {Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer.},
  author       = {Nielsen, Henriette Roed and Nilbert, Mef and Petersen, Janne and Ladelund, Steen and Thomassen, Mads and Pedersen, Inge Søkilde and Hansen, Thomas V O and Skytte, Anne-Bine and Borg, Åke and Therkildsen, Christina},
  issn         = {1389-9600},
  language     = {eng},
  publisher    = {Kluwer},
  series       = {Familial Cancer},
  title        = {BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population.},
  url          = {http://dx.doi.org/10.1007/s10689-016-9875-7},
  year         = {2016},
}