| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Journal of Medical Genetics, 55(1), 15. BMJ Publishing Group |
| ISSN: |
0022-2593 |
| Popis: |
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 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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