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. Issue 1 (10th May 2017)

• Record Type: Journal Article
• Authors: Moghadasi, Setareh; Meeks, Huong D; Vreeswijk, Maaike PG; Janssen, Linda AM; Borg, Åke; Ehrencrona, Hans; Paulsson-Karlsson, Ylva; Wappenschmidt, Barbara; Engel, Christoph; Gehrig, Andrea; Arnold, Norbert; Hansen, Thomas Van Overeem; Thomassen, Mads; Jensen, Uffe Birk; Kruse, Torben A; Ejlertsen, Bent; Gerdes, Anne-Marie; Pedersen, Inge Søkilde; Caputo, Sandrine M; Couch, Fergus; Hallberg, Emily J; van den Ouweland, Ans MW; Collée, Margriet J; Teugels, Erik; Adank, Muriel A; van der Luijt, Rob B; Mensenkamp, Arjen R; Oosterwijk, Jan C; Blok, Marinus J; Janin, Nicolas; Claes, Kathleen BM; Tucker, Kathy; Viassolo, Valeria; Toland, Amanda Ewart; Eccles, Diana E; Devilee, Peter; Van Asperen, Christie J; Spurdle, Amanda B; Goldgar, David E; García, Encarna Gómez;
• Is Part Of: Journal of medical genetics. Volume 55:Issue 1(2018)
• Page Start: 15
• Page End: 20
• Publication Date: 2017-05-10
• Subjects: BRCA1 -- R1699Q -- breastcancer -- ovarian cancer -- intermediate cancer risk -- Surveillance; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2017-104560
• Languages: English
• ISSNs: 1468-6244

Abstract

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.