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

Thesis (Ph.D.)--University of Washington, 2015-12The 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

Enhanced retinal responses in Huntington\u27s disease patients.

BACKGROUND: Huntington\u27s disease (HD) is a fatal progressive neurodegenerative disease characterized by chorea, cognitive impairment and psychiatric symptoms. Retinal examination of HD patients as well as in HD animal models have shown evidence of retinal dysfunction. However, a detailed retinal study employing clinically available measurement tools has not been reported to date in HD. OBJECTIVE: The goal of this study was to assess retinal responses measured by electroretinogram (ERG) between HD patients and controls and evaluate any correlation between ERG measurements and stage of disease. METHODS: Eighteen patients and 10 controls with inclusion criteria of ages 18-70 years (average age HD subjects: 52.1 yrs and control subjects: 51.9 yrs) were recruited for the study. Subjects with previous history of retinal or ophthalmologic disease were excluded. Retinal function was examined by full-field ERG in both eyes of each subject. Amplitudes and latencies to increasing flash intensities in both light- and dark-adaptation were measured in all subjects. Statistical analyses employed generalized estimating equations, which account for repeated measures per subject. RESULTS: We analyzed the b-wave amplitudes of ERG response in all flash intensities and with 30 Hz flicker stimulation. We found statistically significant increased amplitudes in HD patients compared to controls at light-adapted (photopic) 24.2 and 60.9 cd.sec/m2 intensities, dark-adapted (scotopic, red flash) 0.22 cd.sec/m2 intensity, and a trend toward significance at light-adapted 30 Hz flicker. Furthermore, we found a significant increase in light-adapted ERG response from female compared to male HD patients, but no significant difference between gender amongst controls. We also noted a positive association between number of CAG repeats and ERG response at the smallest light adapted intensity (3.1 cd.sec/m2). CONCLUSIONS: ERG studies revealed significantly altered retinal responses at multiple flash intensities in subjects with an HD expansion allele compared to controls. Significant differences were observed with either light-adapted tests or the dark-adapted red flash which suggests that the enhanced responses in HD patients is specific to the cone photoreceptor pathway

A Report on Ten Asia Pacific Countries on Current Status and Future Directions of the Genetic Counseling Profession: The Establishment of the Professional Society of Genetic Counselors in Asia

The Professional Society of Genetic Counselors in Asia (PSGCA) was recently established as a special interest group of the Asia Pacific Society of Human Genetics. Fostering partnerships across the globe, the PSGCA’s vision is to be the lead organization that advances and mainstreams the genetic counseling profession in Asia and ensures individuals have access to genetic counseling services. Its mission is to promote quality genetic counseling services in the region by enhancing practice and curricular standards, research and continuing education. The PSGCA was formally launched during the Genetic Counseling Pre-Conference Workshop held at the 11th Asia-Pacific Conference on Human Genetics in Hanoi, Viet Nam, September 16, 2015. The pre-conference workshop provided an opportunity for medical geneticists and genetic counselors from across 10 Asia Pacific countries to learn about the varied genetic counseling practices and strategies for genetic counseling training. This paper provides an overview of the current status and challenges in these countries, and proposed course of unified actions for the future of the genetic counseling profession