TY - JOUR
T1 - The BRCA1 c. 5096G > A p.Arg1699Gln (R1699Q) intermediate risk variant
T2 - breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
AU - Moghadasi, Setareh
AU - Meeks, Huong D.
AU - Vreeswijk, Maaike P. G.
AU - Janssen, Linda A. M.
AU - Borg, Ake
AU - Ehrencrona, Hans
AU - Paulsson-Karlsson, Ylva
AU - Wappenschmidt, Barbara
AU - Engel, Christoph
AU - Gehrig, Andrea
AU - Arnold, Norbert
AU - Hansen, Thomas Van Overeem
AU - Thomassen, Mads
AU - Jensen, Uffe Birk
AU - Kruse, Torben A.
AU - Ejlertsen, Bent
AU - Gerdes, Anne-Marie
AU - Pedersen, Inge Sokilde
AU - Caputo, Sandrine M.
AU - Couch, Fergus
AU - Hallberg, Emily J.
AU - van den Ouweland, Ans M. W.
AU - Collee, Margriet J.
AU - Teugels, Erik
AU - Adank, Muriel A.
AU - van der Luijt, Rob B.
AU - Mensenkamp, Arjen R.
AU - Oosterwijk, Jan C.
AU - Blok, Marinus J.
AU - Janin, Nicolas
AU - Claes, Kathleen B. M.
AU - Tucker, Kathy
AU - Viassolo, Valeria
AU - Toland, Amanda Ewart
AU - Eccles, Diana E.
AU - Devilee, Peter
AU - Van Asperen, Christie J.
AU - Spurdle, Amanda B.
AU - Goldgar, David E.
AU - Garcia, Encarna Gomez
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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 O ur 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 salpingooophorectomy should be considered based on family history.
AB - 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 O ur 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 salpingooophorectomy should be considered based on family history.
KW - SEQUENCE VARIANTS
KW - CLASSIFICATION
KW - MUTATIONS
U2 - 10.1136/jmedgenet-2017-104560
DO - 10.1136/jmedgenet-2017-104560
M3 - Article
C2 - 28490613
SN - 0022-2593
VL - 55
SP - 15
EP - 20
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 1
ER -