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The BRCA1 c. 5096G > A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands..
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA..
Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands..
Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands..
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2018 (English)In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 55, no 1, p. 15-20Article in journal (Refereed) Published
Abstract [en]

Background: We previously showed that the BRCA1 variant c. 5096G> A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1* R1699Q carriers.

Methods: Data were collected from 129 BRCA1* R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions.

Results: In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83).

Conclusion: O ur results confirm that BRCA1* R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingooophorectomy should be considered based on family history.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP , 2018. Vol. 55, no 1, p. 15-20
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-338982DOI: 10.1136/jmedgenet-2017-104560ISI: 000418199800003PubMedID: 28490613OAI: oai:DiVA.org:uu-338982DiVA, id: diva2:1175486
Available from: 2018-01-18 Created: 2018-01-18 Last updated: 2018-01-18Bibliographically approved

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