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.