Title: CANGENE-CANVAR: data resources, clinical and educational tools to leverage cancer susceptibility genetics for prevention and early detection of cancer
Funder: Cancer Research UK

Abstract: Background Identifying individuals with inherited genetic cancer susceptibility prevents cancer and saves lives through effective targeting of resource for enhanced screening and/or prevention to those at highest a priori risk. Recent advances in sequencing technology have catalysed dramatic expansion in genetic cancer susceptibility testing, with roll-out of population-level screening for cancer susceptibility likely imminent. Aims Our vision is to catalyse UK research, infrastructure development and cancer genetic risk estimation to improve clinical translation. This will ensure coordinated, safe, effective delivery of clinical cancer susceptibility genetics, enabling best outcomes for patients, optimum impact from resources used for saving lives from cancer through screening/prevention and avoidance of harm and litigation through misinterpretation and overdiagnosis. New research resources for analyses of cancer risk and outcomes associated with cancer susceptibility genes (CSGs) Improving accuracy of of risk assessment of all genetic variants in CSGs Consistent evidence-based management of elevated genetic cancer risk across UK clinical settings Empowering participatory patient clinical decision-making around cancer genetic risk Training across broad clinical groups (primary care, oncology clinicians, geneticists) around genetic cancer susceptibility and how best to contextualise and communicate on genetic risk to improve patient care. Methods Generation, release and analyses of pan-UK life-course datasets relating to cancer susceptibility linked to longitudinal Cancer Registry and HES (Hospital Episode Statstics). A national CSG variant data system, available behind the N3-NHS network, housing the national accumulated CSG variant counts, multiple functional datasets, analyses from machine-learning and consensus UK variant interpretations. In partnership with NHS England, development of focused, dynamic, responsive national clinical management protocols for cancer susceptibility through horizon-scanning, literature review, responsive data analyses and clinical consultation. In partnership with patients and the public, to co-create patient-facing Clinical Decision Aids around genetic risk and intervention options. In partnership with Health Education England (HEE), development of hub-and-spoke educational resources on genetic susceptibility and communication of risk, including MOOCs (Massive Open Online Courses). How the results of this research will be used Through the research infrastructure for centralised data linkage, we will generate for tomorrow better evidence regarding cancer genetic risk. In concert, through clinical-facing resources, tools and education we shall ensure the best evidence available today is applied effectively and consistently across our national NHS clinical-laboratory system. This programme of work will create an interface between NHS and research settings that will underpin future expansions in genetic testing access aimed at population risk stratification.

Lay abstract: Background Identifying individuals with inherited genetic cancer susceptibility prevents cancer and saves lives through effective targeting of resource for enhanced screening and/or prevention to those at highest a priori risk. Recent advances in sequencing technology have catalysed dramatic expansion in genetic cancer susceptibility testing, with roll-out of population-level screening for cancer susceptibility likely imminent. Aims Our vision is to catalyse UK research, infrastructure development and cancer genetic risk estimation to improve clinical translation. This will ensure coordinated, safe, effective delivery of clinical cancer susceptibility genetics, enabling best outcomes for patients, optimum impact from resources used for saving lives from cancer through screening/prevention and avoidance of harm and litigation through misinterpretation and overdiagnosis. New research resources for analyses of cancer risk and outcomes associated with cancer susceptibility genes (CSGs) Improving accuracy of of risk assessment of all genetic variants in CSGs Consistent evidence-based management of elevated genetic cancer risk across UK clinical settings Empowering participatory patient clinical decision-making around cancer genetic risk Training across broad clinical groups (primary care, oncology clinicians, geneticists) around genetic cancer susceptibility and how best to contextualise and communicate on genetic risk to improve patient care. Methods Generation, release and analyses of pan-UK life-course datasets relating to cancer susceptibility linked to longitudinal Cancer Registry and HES (Hospital Episode Statstics). A national CSG variant data system, available behind the N3-NHS network, housing the national accumulated CSG variant counts, multiple functional datasets, analyses from machine-learning and consensus UK variant interpretations. In partnership with NHS England, development of focused, dynamic, responsive national clinical management protocols for cancer susceptibility through horizon-scanning, literature review, responsive data analyses and clinical consultation. In partnership with patients and the public, to co-create patient-facing Clinical Decision Aids around genetic risk and intervention options. In partnership with Health Education England (HEE), development of hub-and-spoke educational resources on genetic susceptibility and communication of risk, including MOOCs (Massive Open Online Courses). How the results of this research will be used Through the research infrastructure for centralised data linkage, we will generate for tomorrow better evidence regarding cancer genetic risk. In concert, through clinical-facing resources, tools and education we shall ensure the best evidence available today is applied effectively and consistently across our national NHS clinical-laboratory system. This programme of work will create an interface between NHS and research settings that will underpin future expansions in genetic testing access aimed at population risk stratification.

Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS