Current detection rates and time-to-detection of all identifiable<i>BRCA</i>carriers in the Greater London population.


Manchanda, R; Blyuss, O; Gaba, F; Gordeev, VS; Jacobs, C; Burnell, M; Gan, C; Taylor, R; Turnbull, C; Legood, R; Zaikin, A; Antoniou, AC; Menon, U; Jacobs, I; (2018) Current detection rates and time-to-detection of all identifiable<i>BRCA</i>carriers in the Greater London population. Journal of medical genetics. ISSN 0022-2593 DOI: https://doi.org/10.1136/jmedgenet-2017-105195

[img]
Preview
Text - Accepted Version
License:

Download (758kB) | Preview

Abstract

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

Item Type: Article
Faculty and Department: Faculty of Public Health and Policy > Dept of Health Services Research and Policy
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 29622727
URI: http://researchonline.lshtm.ac.uk/id/eprint/4647297

Statistics


Download activity - last 12 months
Downloads since deposit
26Downloads
36Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item