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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

  • Setareh Moghadasi
  • Huong D. Meeks
  • Maaike P G Vreeswijk
  • Linda A.M. Janssen
  • Åke Borg
  • Hans Ehrencrona
  • Ylva Paulsson-Karlsson
  • Barbara Wappenschmidt
  • Christoph Engel
  • Andrea Gehrig
  • Norbert Arnold
  • Thomas Van Overeem Hansen
  • Mads Thomassen
  • Uffe Birk Jensen
  • Torben A Kruse
  • Bent Ejlertsen
  • Anne-Marie Gerdes
  • Inge Søkilde Pedersen
  • Sandrine M. Caputo
  • Fergus Couch
  • Emily J. Hallberg
  • Ans M W van den Ouweland
  • J Margriet Collée
  • Erik Teugels
  • Muriel A Adank
  • Rob B van der Luijt
  • Arjen R. Mensenkamp
  • Jan C. Oosterwijk
  • Marinus J. Blok
  • Nicolas Janin
  • Kathleen B M Claes
  • Kathy Tucker
  • Valeria Viassolo
  • Amanda Ewart Toland
  • Diana E. Eccles
  • Peter Devilee
  • Christie J. Van Asperen
  • Amanda B Spurdle
  • David E Goldgar
  • Encarna Gómez García
Publishing year: 2017-05-10
Language: English
Publication/Series: Journal of Medical Genetics
Document type: Journal article
Publisher: BMJ Publishing Group

Abstract english

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.


  • Cancer and Oncology


  • ISSN: 0022-2593
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2


Project manager

Familial Breast Cancer



Oncology and Pathology, MV

MV 404 C21C2