TY - JOUR T1 - The <em>BRCA1</em> c. 5096G&gt;A p.Arg1699Gln (R1699Q<span class="underline">)</span> 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 DO - 10.1136/jmedgenet-2017-104560 SP - jmedgenet-2017-104560 AU - Setareh Moghadasi AU - Huong D Meeks AU - Maaike PG Vreeswijk AU - Linda AM Janssen AU - Åke Borg AU - Hans Ehrencrona AU - Ylva Paulsson-Karlsson AU - Barbara Wappenschmidt AU - Christoph Engel AU - Andrea Gehrig AU - Norbert Arnold AU - Thomas Van Overeem Hansen AU - Mads Thomassen AU - Uffe Birk Jensen AU - Torben A Kruse AU - Bent Ejlertsen AU - Anne-Marie Gerdes AU - Inge Søkilde Pedersen AU - Sandrine M Caputo AU - Fergus Couch AU - Emily J Hallberg AU - Ans MW van den Ouweland AU - Margriet J Collée AU - Erik Teugels AU - Muriel A Adank AU - Rob B van der Luijt AU - Arjen R Mensenkamp AU - Jan C Oosterwijk AU - Marinus J Blok AU - Nicolas Janin AU - Kathleen BM Claes AU - Kathy Tucker AU - Valeria Viassolo AU - Amanda Ewart Toland AU - Diana E Eccles AU - Peter Devilee AU - Christie J Van Asperen AU - Amanda B Spurdle AU - David E Goldgar AU - Encarna Gómez García Y1 - 2017/05/10 UR - http://jmg.bmj.com/content/early/2017/05/10/jmedgenet-2017-104560.abstract N2 - 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 salpingo-oophorectomy should be considered based on family history. ER -