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Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population

Manchanda, R; Blyuss, O; Gaba, F; Gordeev, VS; Jacobs, C; Burnell, M; Gan, C; ... Jacobs, I; + view all (2018) Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population. Journal of Medical Genetics , 55 (8) pp. 538-545. 10.1136/jmedgenet-2017-105195. Green open access

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Abstract

BACKGROUND: BRCA carrier identification offers opportunities for early diagnoses, targeted treatment and cancer prevention. We evaluateBRCA-carrier detection rates in general and Ashkenazi Jewish (AJ) populations across Greater London and estimate time-to-detection of all identifiableBRCAcarriers. METHODS: BRCA carrier data from 1993 to 2014 were obtained from National Health Service genetic laboratories and compared with modelled predictions ofBRCAprevalence from published literature and geographical data from UK Office for National Statistics. Proportion ofBRCAcarriers identified was estimated. Prediction models were developed to fitBRCAdetection rate data.BRCAcarrier identification rates were evaluated for an 'Angelina Jolie effect'. Maps for four Greater London regions were constructed, and their relativeBRCAdetection rates were compared. Models developed were used to predict future time-to-identify all detectableBRCAcarriers 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 allBRCAcarriers. Addition of unselected ovarian/triple-negative breast cancer testing would take >250 years to identify allBRCAcarriers. Doubling current detection rates can identify all 'detectable'BRCAcarriers in the general population by year 2181, while parabolic and triple linear rates can identify 'detectable'BRCAcarriers by 2084 and 2093, respectively. The linear fit model can identify 'detectable' AJ carriers by 2044. We did not find an Angelina Jolie effect onBRCAcarrier detection rates. There was a significant difference inBRCAdetection rates between geographical regions over time (P<0.001). CONCLUSIONS: The majority ofBRCAcarriers have not been identified, missing key opportunities for prevention/earlier diagnosis. Enhanced and new strategies/approaches are needed.

Type: Article
Title: Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jmedgenet-2017-105195
Publisher version: https://doi.org/10.1136/jmedgenet-2017-105195
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: BRCA, detection rate, genetic testing, prediction, time to detection
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/10046472
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