The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical ma... - PubMed - NCBI
J Med Genet. 2017 May 10. pii: jmedgenet-2017-104560. doi: 10.1136/jmedgenet-2017-104560. [Epub ahead of print]
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.
Moghadasi S1,
Meeks HD2,
Vreeswijk MP3,
Janssen LA1,
Borg Å4,
Ehrencrona H5,6,
Paulsson-Karlsson Y7,
Wappenschmidt B8,9,10,
Engel C11,12,
Gehrig A13,14,15,
Arnold N16,
Hansen TVO17,18,
Thomassen M19,
Jensen UB20,
Kruse TA19,
Ejlertsen B18,21,
Gerdes AM18,22,
Pedersen IS23,24,
Caputo SM25,
Couch F26,
Hallberg EJ27,
van den Ouweland AM28,
Collée MJ28,
Teugels E29,
Adank MA30,
van der Luijt RB31,32,
Mensenkamp AR33,
Oosterwijk JC34,
Blok MJ35,
Janin N36,
Claes KB37,
Tucker K38,
Viassolo V39,40,
Toland AE41,
Eccles DE42,
Devilee P3,
Van Asperen CJ1,
Spurdle AB43,
Goldgar DE44,
García EG35.
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. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
KEYWORDS:
BRCA1; R1699Q; Surveillance; breastcancer; intermediate cancer risk; ovarian cancer
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