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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
AbstractBACKGROUND:
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...
Show moreAbstractBACKGROUND:
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.
Show less- All authors
- Moghadasi, S.; Meeks, H.D.; Vreeswijk, M.P.G.; Janssen, L.A.M.; Borg, A.; Ehrencrona, H.; Paulsson-Karlsson, Y.; Wappenschmidt, B.; Engel, C.; Gehrig, A.; Arnold, N.; Hansen, T.V.; Thomassen, M.; Jensen, U.B.; Kruse, T.A.; Ejlertsen, B.; Gerdes, A.M.; Pedersen, I.S.; Caputo, S.M.; Couch, F.; Hallberg, E.J.; Ouweland, A.M.W. van den; Collee, M.J.; Teugels, E.; Adank, M.A.; Luijt, R.B. van der; Mensenkamp, A.R.; Oosterwijk, J.C.; Blok, M.J.; Janin, N.; Claes, K.B.M.; Tucker, K.; Viassolo, V.; Toland, A.E.; Eccles, D.E.; Devilee, P.; Asperen, C.J. van; Spurdle, A.B.; Goldgar, D.E.; Garcia, E.G.
- Date
- 2017-05-10
- Journal
- Journal of Medical Genetics