Grant Number:	1R01CA303649-01A1 Interpret this number
Primary Investigator:	Katz, Steven
Organization:	University Of Michigan At Ann Arbor
Project Title:	Virtual Solutions to Reduce Gaps in Genetic Risk Evaluation and Management in Families with Hereditary Cancer Syndromes: the Genetic Information and Family Testing (Gift 2) Study
Fiscal Year:	2026

Cascade genetic risk evaluation (GRE) can saves lives lost to hereditary cancers. Yet, we are failing patients and their families with hereditary cancer syndromes (HCS), as fewer than one quarter of at-risk relatives receive cascade testing. We pioneered the Georgia California SEER Genetic Testing Linkage Initiative (GACA Linkage) that linked genetic testing results from laboratory partners to the SEER clinical database for all adults diagnosed with cancer and reported to the registries of Georgia and California from 2013-2019 with test results accessed through 2022. We completed the Genetic Information and Family Testing (GIFT 1) study that implemented a virtual platform (the Family Genetic Health Program, FGHP) for patients and relatives to increase cascade genetic risk evaluation in families with HCS. We have updated the GACA Linkage data infrastructure to include all patients diagnosed with cancer in the two states through 2024, with genetic test results accessed through 2025. We will select a new patient sample from this cohort to implement the GIFT 2 Study: a pragmatic, registry-based clinical trial to implement and evaluate a next- generation, virtual AI-assisted Family Genetic Health Platform (FGHP-AI) that delivers personalized genetic risk education with the choice of low-cost, at-home genetic testing for families with HCS. The goal of GIFT 2 is to determine the optimal strategy for incorporating an AI assistant into the FGHP platform to optimize communication and engagement between patients and their relatives to maximize uptake of cascade cancer genetic risk evaluation including at-home testing. GIFT 2 will determine if FGHP-AI (study design feature, intervention arm) is superior to FGHP-C used and evaluated in GIFT 1 (control arm). We will select all adults diagnosed with cancer in 2023-24 in Georgia and California in whom a clinically meaningful pathogenic variant (PV) was detected on germline testing (N=3,780) and invite them to our online cancer family genetic health education program. Patients will be screened for trial eligibility (recall of a PV result on germline testing), and those eligible will be immediately invited to enroll in GIFT 2. Enrolled patients will use the GIFT platform to invite eligible relatives to the study. Invited relatives will enroll in the study directly through the platform to receive genetic risk education and the choice of at-home genetic testing at a low cost of $50. Patients and their family cluster will be randomized post consent to two trial arms: FGHP-AI vs. FGHP-C. The specific aims are to determine the effect of FGHP-AI (intervention arm) vs FGHP-C (control arm) on: 1) the cancer patient’s appraisal of communication and engagement with relatives about hereditary cancer and genetic risk evaluation; 2) the invited relative’s receipt of genetic testing (primary outcome); and 3) the enrolled relative’s appraisal of decision-making and completion of formal genetic risk evaluation in their healthcare system. The findings of this study have enormous potential to improve cancer prevention and early detection in families with hereditary cancer syndromes to reduce the burden of cancer in the US.