RT Journal Article
SR Electronic
T1 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
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP jmedgenet-2017-104560
DO 10.1136/jmedgenet-2017-104560
A1 Setareh Moghadasi
A1 Huong D Meeks
A1 Maaike PG Vreeswijk
A1 Linda AM Janssen
A1 Åke Borg
A1 Hans Ehrencrona
A1 Ylva Paulsson-Karlsson
A1 Barbara Wappenschmidt
A1 Christoph Engel
A1 Andrea Gehrig
A1 Norbert Arnold
A1 Thomas Van Overeem Hansen
A1 Mads Thomassen
A1 Uffe Birk Jensen
A1 Torben A Kruse
A1 Bent Ejlertsen
A1 Anne-Marie Gerdes
A1 Inge Søkilde Pedersen
A1 Sandrine M Caputo
A1 Fergus Couch
A1 Emily J Hallberg
A1 Ans MW van den Ouweland
A1 Margriet J Collée
A1 Erik Teugels
A1 Muriel A Adank
A1 Rob B van der Luijt
A1 Arjen R Mensenkamp
A1 Jan C Oosterwijk
A1 Marinus J Blok
A1 Nicolas Janin
A1 Kathleen BM Claes
A1 Kathy Tucker
A1 Valeria Viassolo
A1 Amanda Ewart Toland
A1 Diana E Eccles
A1 Peter Devilee
A1 Christie J Van Asperen
A1 Amanda B Spurdle
A1 David E Goldgar
A1 Encarna Gómez García
YR 2017
UL http://jmg.bmj.com/content/early/2017/05/10/jmedgenet-2017-104560.abstract
AB 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.