Abstract
Health care providers need simple tools to identify patients at genetic risk of breast and ovarian cancers. Genetic risk prediction models such as BRCAPRO could fill this gap if incorporated into Electronic Medical Records or other Health Information Technology solutions. However, BRCAPRO requires potentially extensive information on the counselee and her family history. Thus, it may be useful to provide simplified version(s) of BRCAPRO for use in settings that do not require exhaustive genetic counseling. We explore four simplified versions of BRCAPRO, each using less complete information than the original model. BRCAPROLYTE uses information on affected relatives only up to second degree. It is in clinical use but has not been evaluated. BRCAPROLYTE-Plus extends BRCAPROLYTE by imputing the ages of unaffected relatives. BRCAPROLYTE-Simple reduces the data collection burden associated with BRCAPROLYTE and BRCAPROLYTE-Plus by not collecting the family structure. BRCAPRO-1Degree only uses first-degree affected relatives. We use data on 2,713 individuals from seven sites of the Cancer Genetics Network and MD Anderson Cancer Center to compare these simplified tools with the Family History Assessment Tool (FHAT) and BRCAPRO, with the latter serving as the benchmark. BRCAPROLYTE retains high discrimination; however, because it ignores information on unaffected relatives, it overestimates carrier probabilities. BRCAPROLYTE-Plus and BRCAPROLYTE-Simple provide better calibration than BRCAPROLYTE, so they have higher specificity for similar values of sensitivity. BRCAPROLYTE-Plus performs slightly better than BRCAPROLYTE-Simple. The Areas Under the ROC curve are 0.783 (BRCAPRO), 0.763 (BRCAPROLYTE), 0.772 (BRCAPROLYTE-Plus), 0.773 (BRCAPROLYTE-Simple), 0.728 (BRCAPRO-1Degree), and 0.745 (FHAT). The simpler versions, especially BRCAPROLYTE-Plus and BRCAPROLYTE-Simple, lead to only modest loss in overall discrimination compared to BRCAPRO in this dataset. Thus, we conclude that simplified implementations of BRCAPRO can be used for genetic risk prediction in settings where collection of complete pedigree information is impractical.
Highlights
Carriers of deleterious mutations of the BRCA1 and BRCA2 genes are at a much higher lifetime risk of developing breast and ovarian cancers than the general population [1, 2], and may benefit from more intensive screening, prophylactic surgery, and/or chemoprevention [3]
We use data on 2713 individuals from seven sites of the Cancer Genetics Network and MD Anderson Cancer Center to compare these simplified tools with the Family History Assessment Tool (FHAT) and BRCAPRO, with the latter serving as the benchmark
The simpler versions, especially BRCAPROLYTEPlus and BRCAPROLYTE-Simple, lead to only modest loss in overall discrimination compared to BRCAPRO in this dataset
Summary
Carriers of deleterious mutations of the BRCA1 and BRCA2 genes are at a much higher lifetime risk of developing breast and ovarian cancers than the general population [1, 2], and may benefit from more intensive screening, prophylactic surgery, and/or chemoprevention [3]. A majority of mutation carriers remain unaware of their status and risk, and are not managed in a way that might mitigate their risk [4] This is partly because health care providers lack tools that can help them efficiently identify high-risk patients within the time and resource constraints of a busy practice. Genetic risk prediction models used currently in genetic counseling could help fill this gap if adapted and incorporated into Electronic Medical Records (EMR) or other Health Information Technology (HIT) solutions [5]. Such adaptation could play a central role in identifying potential carriers so that they can be referred for risk assessment, genetic testing, and appropriate management. An example, named BRCAPROLYTE, is implemented in HRA [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
