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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

Moghadasi, Setareh ; Meeks, Huong D. ; Vreeswijk, Maaike P G ; Janssen, Linda A.M. ; Borg, Åke LU ; Ehrencrona, Hans LU orcid ; Paulsson-Karlsson, Ylva ; Wappenschmidt, Barbara ; Engel, Christoph and Gehrig, Andrea , et al. (2018) In Journal of Medical Genetics 55(1). p.15-20
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... (More)

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 Our 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medical Genetics
volume
55
issue
1
pages
15 - 20
publisher
BMJ Publishing Group
external identifiers
  • scopus:85027525900
  • pmid:28490613
  • wos:000418199800003
ISSN
0022-2593
DOI
10.1136/jmedgenet-2017-104560
language
English
LU publication?
yes
id
49c9bd1c-c6fa-482d-b759-48b1fbe9c9d2
date added to LUP
2017-09-04 11:52:58
date last changed
2025-03-19 06:49:58
@article{49c9bd1c-c6fa-482d-b759-48b1fbe9c9d2,
  abstract     = {{<p>Background We previously showed that the BRCA1 variant c.5096G&gt;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 Our 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.</p>}},
  author       = {{Moghadasi, Setareh and Meeks, Huong D. and Vreeswijk, Maaike P G and Janssen, Linda A.M. and Borg, Åke and Ehrencrona, Hans and Paulsson-Karlsson, Ylva and Wappenschmidt, Barbara and Engel, Christoph and Gehrig, Andrea and Arnold, Norbert and Van Overeem Hansen, Thomas and Thomassen, Mads and Jensen, Uffe Birk and Kruse, Torben A and Ejlertsen, Bent and Gerdes, Anne-Marie and Pedersen, Inge Søkilde and Caputo, Sandrine M. and Couch, Fergus and Hallberg, Emily J. and van den Ouweland, Ans M W and Collée, J Margriet and Teugels, Erik and Adank, Muriel A and van der Luijt, Rob B and Mensenkamp, Arjen R. and Oosterwijk, Jan C. and Blok, Marinus J. and Janin, Nicolas and Claes, Kathleen B M and Tucker, Kathy and Viassolo, Valeria and Toland, Amanda Ewart and Eccles, Diana E. and Devilee, Peter and Van Asperen, Christie J. and Spurdle, Amanda B and Goldgar, David E and García, Encarna Gómez}},
  issn         = {{0022-2593}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{15--20}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Journal of Medical Genetics}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1136/jmedgenet-2017-104560}},
  doi          = {{10.1136/jmedgenet-2017-104560}},
  volume       = {{55}},
  year         = {{2018}},
}