Background BRCA carrier identification offers opportunities for early diagnoses, targeted treatment and cancer prevention. We evaluate BRCA- carrier detection rates in general and Ashkenazi Jewish (AJ) populations across Greater London and estimate time-to-detection of all identifiable BRCA carriers.
Methods BRCA carrier data from 1993 to 2014 were obtained from National Health Service genetic laboratories and compared with modelled predictions of BRCA prevalence from published literature and geographical data from UK Office for National Statistics. Proportion of BRCA carriers identified was estimated. Prediction models were developed to fit BRCA detection rate data. BRCA carrier identification rates were evaluated for an ‘Angelina Jolie effect’. Maps for four Greater London regions were constructed, and their relative BRCA detection rates were compared. Models developed were used to predict future time-to-identify all detectable BRCA carriers in AJ and general populations.
Results Until 2014, only 2.6% (3072/111 742 estimated) general population and 10.9% (548/4985 estimated) AJ population BRCA carriers have been identified in 16 696 608 (AJ=190 997) Greater London population. 57% general population and 54% AJ mutations were identified through cascade testing. Current detection rates mirror linear fit rather than parabolic model and will not identify all BRCA carriers. Addition of unselected ovarian/triple-negative breast cancer testing would take >250 years to identify all BRCA carriers. Doubling current detection rates can identify all ‘detectable’ BRCA carriers in the general population by year 2181, while parabolic and triple linear rates can identify ‘detectable’ BRCA carriers by 2084 and 2093, respectively. The linear fit model can identify ‘detectable’ AJ carriers by 2044. We did not find an Angelina Jolie effect on BRCA carrier detection rates. There was a significant difference in BRCA detection rates between geographical regions over time (P<0.001).
Conclusions The majority of BRCA carriers have not been identified, missing key opportunities for prevention/earlier diagnosis. Enhanced and new strategies/approaches are needed.
- genetic testing
- time to detection
- detection rate
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Contributors RM developed the concept and design of the study. RM, RT, CJ, FG, CG, OB, AZ, VSG, MB and IJ were involved in conduct of the study. RT and CJ contributed data to the study. FG and CG helped with data collection. OB, AZ and RM developed the models. RM, OB, FG, VSG, AZ and MB contributed to data analysis and preparation of figures and tables. RM and OB prepared the initial draft of the manuscript. All authors contributed to reporting of the work, including paper writing and critical review of the analysis. All authors approved the final version of the manuscript. RM and OB are guarantors of the work.
Funding The study was in part funded by ‘The Eve Appeal’ charity (GTCV).
Disclaimer The funding body (The Eve Appeal charity) had no role in the study design, data collection, analysis, interpretation, writing of the report or decision to submit for publication. The research team was independent of funders.
Competing interests IJ and UM have a financial interest in Abcodia, Ltd, a company formed to develop academic and commercial development of biomarkers for screening and risk prediction. IJ is a member of the board of Abcodia Ltd, a Director of Women’s Health Specialists Ltd and received consultancy from Beckton Dickinson. RM declares research funding from The Eve Appeal and Cancer Research UK into population testing and from Barts & the London Charity outside this work, as well as an honorarium for grant review from Israel National Institute for Health Policy Research. The other authors declare no conflict of interest.
Patient consent Not required.
Ethics approval This analysis was approved under the ethics approval obtained for the Genetic Cancer Prediction through Population Screening (GCaPPS) study from the Institute of Child Health/ Great Ormond Street Hospital Research Ethics Committee: REC Reference number 08/H0713/44.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Relevant anonymised data can be obtained on reasonable request from the corresponding author.
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