A two-stage approach to genetic risk assessment in primary care.
Genetic risk prediction models such as BRCAPRO are used routinely in genetic counseling for identification of potential BRCA1 and BRCA2 mutation carriers. They require extensive information on the counselee and her family history, and thus are not practical for primary care. To address this gap, we develop and test a two-stage approach to genetic risk assessment by balancing the tradeoff between the amount of information used and accuracy achieved. The first stage is intended for primary care wherein limited information is collected and analyzed using a simplified version of BRCAPRO. If the assessed risk is sufficiently high, more extensive information is collected and the full BRCAPRO is used (stage two: intended for genetic counseling). We consider three first-stage tools: BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple. We evaluate the two-stage approach on independent clinical data on probands with family history of breast and ovarian cancers, and BRCA genetic test results. These include population-based data on 1344 probands from Newton-Wellesley Hospital and mostly high-risk family data on 2713 probands from Cancer Genetics Network and MD Anderson Cancer Center. We use discrimination and calibration measures, appropriately modified to evaluate the overall performance of a two-stage approach. We find that the proposed two-stage approach has very limited loss of discrimination and comparable calibration as BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. We conclude that the two-stage approach allows for practical large-scale genetic risk assessment in primary care.
['Biswas|Swati|S|', 'Atienza|Philamer|P|', 'Chipman|Jonathan|J|', 'Blackford|Amanda L|AL|', 'Arun|Banu|B|', 'Hughes|Kevin|K|', 'Parmigiani|Giovanni|G|']
D019313:BRCA1 Protein D024682:BRCA2 Protein D001943:Breast Neoplasms D005260:Female D005817:Genetic Counseling D020022:Genetic Predisposition to Disease D006801:Humans D008297:Male D008875:Middle Aged D009154:Mutation D010051:Ovarian Neoplasms D010375:Pedigree D011320:Primary Health Care D012189:Retrospective Studies D018570:Risk Assessment D012307:Risk Factors
BRCAPRO BRCA1 BRCA2 BayesMendel CancerGene