Use this URL to cite or link to this record in EThOS:
Title: A population based approach to genetic testing for cancer risk prediction and management
Author: Manchanda, R.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Genetic testing for high-penetrance cancer predisposing mutations is currently only accessible to individuals with a strong family-history (FH). This misses a number of at-risk individuals. Limitations to this approach could be overcome by population-based testing. This research evaluates the feasibility and impact of population-screening (PS) for inheritable cancer by comparing it with the standard FH-based approach. The Ashkenazi Jewish (AJ) population is used as a 'population model' and BRCA1/2 mutations as a 'disease model'. The study design involves a randomised trial called: GCaPPS. Inclusion criteria: (a) AJ ethnicity, (b) age 18 years. Exclusion criteria: (a) first-degree-relative BRCA-carriers (b) prior BRCA testing. Outcomes: (a) BRCA carriers, (b) acceptability, (c) psychological, quality-of-life impact (d) uptake of screening/preventive options (e) health-economics. All participants underwent pre-test genetic counselling (DVD-based/ traditional face-to-face). All PS- arm participants and those fulfilling standard criteria in FH-arm underwent genetic testing. This thesis describes the development, design, recruitment and outcome of the trial to 3-months follow-up. 1034 participants were randomised to FH(504)/ PS(530) arms. Their mean/median age was 54.3(SD14.66)/56(IQR43,65) years; 33.2% were men and 66.8% women. 72% of registered people attended genetic-counselling, 40% attendees indicated clear intention-to-test and 89% consented to genetic-testing. 13-carriers were identified in PS (7BRCA1, 6BRCA2), 9 in FH (5BRCA1, 4BRCA2) arms (p=0.522) and a further 5-carriers in FH-negative participants in FH-arm following study completion. 56% carriers in the entire cohort were missed by FH compared to PS. FH had poor ability to predict (positive likelihood-ratio=3.86) or rule out (negative likelihood-ratio=0.63) a mutation. BRCA1/2 prevalence is 2.45%(CI:1.31%,4.16%): 1.16%(C1:0.60°/0,2.02%) for FH-positive and 1.89%(CI:0.91%,3.44%) for FH-negative carriers. There was no difference at 7-days/ 3-months for outcomes of anxiety, depression, quality-of-life, health-anxiety, distress and uncertainty between population-based and FH-based testing. DVD-based counselling halved counselling time (p<0.0005), led to cost minimisation of £14/volunteer, without affecting counselling satisfaction (p=0.468) or increase in knowledge (p=0.174) compared to standard counselling. Probabilistic-sensitivity-analysis indicated PS is highly cost- effective in 92% simulations, with an incremental cost-effectiveness-ratio of £499/QALY, equating to 21days gain in life- expectancy, and 0.37% reduction in ovarian cancer incidence. These findings provide strong arguments for further exploration of a new paradigm of population-based testing for BRCA1/2 and other germ line mutations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available