title: Multi-gene panel testing for hereditary cancer susceptibility in a rural Familial Cancer Program.
abstract: This study explores our Familial Cancer Program's experience implementing multi-gene panel testing in a largely rural patient population. We conducted a retrospective review of patients undergoing panel testing between May 2011 and August 2015. Our goal was to evaluate factors that might be predictors of identifying variants (pathogenic or uncertain significance) and to assess clinical management changes due to testing. We utilized a structured family history tool to determine the significance of patient's family histories with respect to identification of genetic variants. A total of 227 patients underwent panel testing at our center and 67 patients (29.5 %) had variants identified, with 8 (3.5 %) having multiple variants. Overall, 44 patients (19.4 %) had a variant of uncertain significance (VUS) and 28 patients (12.3 %) had a pathogenic variant detected, with 10 (4.4 %) having pathogenic variants in highly penetrant genes. We found no statistical difference in patient familial and personal cancer history, age, rural status, Ashkenazi Jewish ancestry, insurance coverage and prior single-gene testing among those with pathogenic, VUS and negative panel testing results. There were no predictors of pathogenic variants on regression analysis. Panel testing changed cancer screening and management guidelines from that expected based on family history alone in 13.2 % of patients. Ultimately, cancer panel testing does yield critical information not identified by traditional single gene testing but maximal utility through a broad range of personal and family histories requires improved interpretation of variants.
authors.affiliation: Department of Medicine and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Ave, Given E214, Burlington, VT, 05405, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hermel
authors.affiliation: Department of Medicine and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Ave, Given E214, Burlington, VT, 05405, USA.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: McKinnon
authors.affiliation: Department of Medicine and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Ave, Given E214, Burlington, VT, 05405, USA.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Wood
authors.affiliation: Department of Medicine and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Ave, Given E214, Burlington, VT, 05405, USA. Marc.Greenblatt@uvmhealth.edu.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Greenblatt
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D012189:Retrospective Studies; D012424:Rural Population
keywords: Cancer genetics; Familial and hereditary cancers; Genetic cancer assessment; Genetic counseling; Multigene panels; Multiplex testing