Moghadasi, Setareh, Meeks, Huong D., Vreeswijk, Maaike P. G., Janssen, Linda A. M., Borg, Ake, Ehrencrona, Hans ORCID: 0000-0002-5589-3622, Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara, Engel, Christoph ORCID: 0000-0002-7247-282X, Gehrig, Andrea, Arnold, Norbert ORCID: 0000-0003-4523-8808, Hansen, Thomas Van Overeem, Thomassen, Mads, Jensen, Uffe Birk ORCID: 0000-0002-6205-6355, Kruse, Torben A., Ejlertsen, Bent, Gerdes, Anne-Marie ORCID: 0000-0002-0328-3320, Pedersen, Inge Sokilde, Caputo, Sandrine M., Couch, Fergus, Hallberg, Emily J., van den Ouweland, Ans M. W., Collee, Margriet J., Teugels, Erik ORCID: 0000-0002-7828-4555, Adank, Muriel A., van der Luijt, Rob B., Mensenkamp, Arjen R., Oosterwijk, Jan C., Blok, Marinus J., Janin, Nicolas, Claes, Kathleen B. M., Tucker, Kathy, Viassolo, Valeria, Toland, Amanda Ewart, Eccles, Diana E., Devilee, Peter ORCID: 0000-0002-8023-2009, Van Asperen, Christie J., Spurdle, Amanda B., Goldgar, David E. and Garcia, Encarna Gomez (2018). 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. J. Med. Genet., 55 (1). S. 15 - 21. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-6244

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Moghadasi, SetarehUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meeks, Huong D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vreeswijk, Maaike P. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janssen, Linda A. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borg, AkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ehrencrona, HansUNSPECIFIEDorcid.org/0000-0002-5589-3622UNSPECIFIED
Paulsson-Karlsson, YlvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wappenschmidt, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engel, ChristophUNSPECIFIEDorcid.org/0000-0002-7247-282XUNSPECIFIED
Gehrig, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, NorbertUNSPECIFIEDorcid.org/0000-0003-4523-8808UNSPECIFIED
Hansen, Thomas Van OvereemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomassen, MadsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, Uffe BirkUNSPECIFIEDorcid.org/0000-0002-6205-6355UNSPECIFIED
Kruse, Torben A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ejlertsen, BentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerdes, Anne-MarieUNSPECIFIEDorcid.org/0000-0002-0328-3320UNSPECIFIED
Pedersen, Inge SokildeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caputo, Sandrine M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, FergusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallberg, Emily J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Ouweland, Ans M. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collee, Margriet J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teugels, ErikUNSPECIFIEDorcid.org/0000-0002-7828-4555UNSPECIFIED
Adank, Muriel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Luijt, Rob B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mensenkamp, Arjen R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oosterwijk, Jan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blok, Marinus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janin, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Claes, Kathleen B. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tucker, KathyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Viassolo, ValeriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toland, Amanda EwartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eccles, Diana E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devilee, PeterUNSPECIFIEDorcid.org/0000-0002-8023-2009UNSPECIFIED
Van Asperen, Christie J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spurdle, Amanda B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldgar, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia, Encarna GomezUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-200666
DOI: 10.1136/jmedgenet-2017-104560
Journal or Publication Title: J. Med. Genet.
Volume: 55
Number: 1
Page Range: S. 15 - 21
Date: 2018
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-6244
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SEQUENCE VARIANTS; CLASSIFICATION; MUTATIONSMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/20066

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