The Return of Genetic Research Results in the Context of an International Colon Cancer Family Registry

Abstract

The overall aim of this dissertation study was to describe the experience of the Colon Cancer Family Registry (C-CFR) with return of results (ROR) from genetic research and to document site-specific ROR outcomes. The C-CFR is comprised of six registry sites: the University of Hawaii, Honolulu, HI (HI); the Mayo Clinic, Rochester, MN (MA); the Fred Hutchinson Cancer Research Center, Seattle, WA (SE); the University of Southern California, Consortium, Los Angeles, CA (USC); the Cancer Care Ontario, Canada (ON); and the University of Melbourne, Melbourne, Australia (AU). Registry site-specific experiences with ROR and ROR-related outcomes were explored using a mixed-methods study design. For Specific Aim 1, qualitative interviews with 14 registry investigators and staff from the six C-CFR sites demonstrated the complexity of ROR protocol development and implementation in practice. Thematic analysis from the interviews identified three main factors underlying site-specific ROR protocol and implementation differences: 1) the training and prior experience of C-CFR staff, 2) access to a robust public health infrastructure, and 3) the influence of local regulatory norms and/or informed consent. For Specific Aim 2, multivariable logistic regression model analysis of the association between acceptance of Lynch Syndrome (LS) genetic research results and participant demographic characteristics had identified the participant’s age, marital status, and race/ethnicity as significantly associated with the likelihood of LS genetic research result acceptance. Overall, the proportion of participants accepting LS genetic research results among the SE, HI, MA and AU C-CFR sites was 63% (481/763). For Specific Aim 3, a sequential mixed-methods investigation of Seattle C-CFR participants approached for LS-related ROR explored post-disclosure result clinical validation and sharing of results with family members and health care providers. Twenty-six of 34 SE C-CFR participants (76.5%) who accepted non-CLIA genetic research results completed a survey 12 months post disclosure. Of these, 4 (15.4%) reported having clinically verified their non-CLIA genetic research results, 22 (84.6%) reported having shared the results with family members, and 15 (57.7%) participants shared with their health care providers. Follow-up qualitative interviews with a subset of these participants found that acting on the recommendation of the research team and informing future clinical care were the main reasons given for pursuing clinical verification. Participants who did not verify their results cited lack of insurance coverage and limited perceived personal and/or clinical benefits as relevant reasons to their decision. From the experience of a multi-site international research cancer registry, results from this dissertation study provide valuable insights into the complexity of ROR protocol development and implementation, as well as the potential impact of genetic research result return on participants and their families. As such, these study findings should help guide future policy development regarding the return of individual results from genetic research in related settings.