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, Pg Maaike 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 CouchEmily J. Hallberg, Ans M.W. Van Den Ouweland, Margriet J. Collée, Erik Teugels, Muriel A. Adank, Rob B. Van Der Luijt, R. Arjen 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

Research output: Contribution to journalArticle

24 Scopus citations

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 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 salpingo-oophorectomy should be considered based on family history.

Original languageEnglish (US)
Pages (from-to)15-20
Number of pages6
JournalJournal of medical genetics
Volume55
Issue number1
DOIs
StatePublished - Jan 2018

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Moghadasi, S., Meeks, H. D., Vreeswijk, P. M., Janssen, L. A. M., Borg, Å., Ehrencrona, H., Paulsson-Karlsson, Y., Wappenschmidt, B., Engel, C., Gehrig, A., Arnold, N., Van Overeem Hansen, T., Thomassen, M., Jensen, U. B., Kruse, T. A., Ejlertsen, B., Gerdes, A. M., Pedersen, I. S., Caputo, S. M., ... García, E. G. (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. Journal of medical genetics, 55(1), 15-20. https://doi.org/10.1136/jmedgenet-2017-104560