Thec. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant : breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
Moghadasi, Setareh; Meeks, Huong D.; Vreeswijk, Maaike P G; Janssen, Linda A.M.; Borg, Åke; Ehrencrona, Hans; Paulsson-Karlsson, Ylva; Wappenschmidt, Barbara; Engel, Christoph; Gehrig, Andrea; Arnold, Norbert; Van Overeem Hansen, Thomas; Thomassen, Mads; Jensen, Uffe Birk; Kruse, Torben A.; Ejlertsen, Bent; Gerdes, Anne Marie; Pedersen, Inge Søkilde; Caputo, Sandrine M.; Couch, Fergus J.; Hallberg, Emily J.; Van Den Ouweland, Ans M W; Collée, J. Margriet; Teugels, Erik; Adank, Muriel A.; van der Luijt, Rob B.; Mensenkamp, Arjen R.; Oosterwijk, Jan C.; Blok, Marinus J.; Janin, Nicolas; Claes, Kathleen B M; 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
(2018) Journal of Medical Genetics, volume 55, issue 1, pp. 15 - 20
(Article)
Abstract
BACKGROUND: We previously showed that theBRCA1variant 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
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to propose adjusted clinical management of femaleBRCA1*R1699Q carriers. METHODS: Data were collected from 129BRCA1*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 thatBRCA1*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.
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Author keywords: Genetics, Genetics(clinical), Journal Article
ISSN: 0022-2593
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