A population-based virtual solution to reduce gaps in genetic risk evaluation and management in families at high risk for hereditary cancer syndromes: The Georgia-California GeneLINK Trial

基于人群的虚拟解决方案，可缩小遗传性癌症综合征高风险家庭遗传风险评估和管理方面的差距：佐治亚州-加利福尼亚州 GeneLINK 试验

• 批准号: 10469681
• 负责人: Lawrence Chin-I An
• 金额: $ 75.09万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469681
• 关键词: Adult; Affect; Attitude; California; Cancer Burden; Cancer Patient; Cancer-Predisposing Gene; Clinical; Communication; Communication Tools; Communities; Complex; Conflict (Psychology); Counseling; Decision Making; Diagnosis; Early Diagnosis; Education; Enrollment; Evaluation; Family; Family member; Future; Genetic; Genetic Counseling; Genetic Risk; Guidelines; Health; Hereditary Malignant Neoplasm; Hereditary Neoplastic Syndromes; Human; Incentives; Intervention Trial; Malignant Neoplasms; Medical; Outcome; Pathogenicity; Patients; Population; Positioning Attribute; Prevention; Prevention strategy; Price; Professional counselor; Randomized; Relative Risks; Reporting; Resources; Risk Reduction; Sampling; Screening for cancer; Second Degree Relative; Services; Specialist; Subgroup; Technology; Test Result; Testing; Variant; cancer diagnosis; cancer prevention; cancer risk; clinically actionable; clinically relevant; clinically significant; cohort; contextual factors; cost; cost effective; data infrastructure; design; evaluation/testing; family genetics; genetic panel test; genetic testing; health care disparity; high risk; improved; individualized prevention; interest; neoplasm registry; novel strategies; population based; practical application; precision genetics; precision oncology; primary outcome; programs; randomized trial; social factors; therapy design; tool; virtual; virtual platform

Project Abstract: There is growing evidence that targeting genetic risk evaluation (GRE) in families where a cancer susceptibility gene pathogenic variant (PV) has been identified may be the most cost-effective approach to reduce the population burden of cancer through prevention. However, there are enormous challenges to implementing successful cascade genetic risk evaluation in families with hereditary cancer syndromes. The clinical context of GRE after cancer diagnosis is increasingly complex: As MGP testing has become the norm, guideline organizations have converged on a list of >40 cancer susceptibility genes in which PVs are clinically actionable, with wide variability in cancer threat and a myriad of strategies for prevention and early detection. A daunting challenge is that the cancer patient is responsible for communication and engagement of relatives for GRE. Despite the shared health threat among at risk relatives (ARRs), the social and contextual factors that affect family communication are complex. Furthermore, ARRs are dispersed world- wide and receive care in disparate health care practices. Importantly, there is little incentive and limited resources for clinicians to engage cancer patients’ relatives and genetic counseling services are increasingly strained. Given the lack of guidance for families, it is not surprising that most ARRs of cancer patients with PVs do not undergo GRE. We are uniquely positioned to develop and optimize a direct-to-family virtual genetic risk evaluation and testing solution offered to all at risk relatives of a population-based sample of adults recently diagnosed with cancer in Georgia and California who tested positive for a clinically relevant PV. We will use a unique data infrastructure we pioneered to identify and invite a diverse cohort of cancer patients with clinically relevant PVs and their families to participate in our study. We propose a 2 x 3 factorial randomized trial of 900 patients diagnosed in 2018-2019 in the two states who had a clinically significant PV detected by genetic testing that will offer genetic risk evaluation and testing to all 1st and 2nd degree relatives. We will evaluate the effects of two intervention design features on patient- and relative-centered outcomes: 1) the level of personalized family genetic risk support (a technology assisted personally tailored patient and family member education and communication tool called the Family Genetic Health Program, FGHP) vs. the FGHP plus direct assistance from a human FGHP Navigator); and 2) the price offered to the relatives for the genetic test (standard $200 vs. $100 vs. $50 per test). We will determine the independent effects of the two design features on 1) the cancer patient’s appraisal of communication and their engagement with relatives about hereditary cancer and GRE; 2) the invited relative’s appraisal of decision-making and receipt of genetic testing; and 3) on the enrolled relative’s completion of formal GRE. We will also explore the effect of the features on the outcomes across patient SES subgroups. The findings of this study have enormous potential to improve cancer prevention and early detection in families at high risk of hereditary cancer syndromes in the US.

项目摘要：越来越多的证据表明，针对遗传风险评估（GRE）的家庭有一个