The Health Outcomes, Utility, and Costs of Returning Incidental Genomic Findings

Background

Genomic sequencing (GS) is considered the 'next step' towards personalized medicine, providing an opportunity to improve the prevention, diagnosis and treatment of disease. Across Canada, clinicians are increasingly using GS to identify treatments and management approaches likely to benefit patients based on molecular makeup, especially in oncology. GS offers increased sensitivity over classic genetic tests. For example, multi-gene sequencing has been shown to increase the sensitivity of identifying clinically actionable mutations in breast cancer patients by 50% to 60% when compared to testing for BRCA1/2 alone. Often breast cancer patients who test negative for BRCA1/2 will be offered GS to identify causative mutations. In addition, GS can also be used to analyze the molecular profile of a patient's tumour (somatic GS) to identify therapeutic targets.

However, the process of decoding the genome an individual or their tumour may incidentally reveal information about inherited predispositions to other cancers and diseases, including genetic variants/changes associated with current (undiagnosed) disease, drug response, risk for future diseases and variants of unknown clinical significance. Increasing policy guidance suggests that 'medically actionable' results should be offered to patients undergoing clinical sequencing, with calls to offer additional incidental results based on patient preferences. There is limited evidence on the psychological harms and clinical benefits of returning incidental GS results to patients.

Psychological distress: Single-gene and multiplex testing for hereditary cancers, neurological and cardiac disease appears to have minimal psychological impacts. A recent study found that few participants report distress from GS results. However, these findings are based on individuals who agreed to be tested for particular genes, and were prepared through counseling or otherwise to receive these results. This may not translate to incidentally-discovered genetic risk, which individuals did not anticipate or choose to learn a priori. Distress related to receiving incidental GS results remains unknown.

Personal utility: Studies suggest that individuals want to learn their GS results because they expect them to offer 'personal utility'. Personal utility is considered an increasingly important precursor of clinical utility, which is believed to offer richer self-knowledge and motivate risk reducing behaviors. Most studies focus on the hypothetical return of incidental GS results, little is known about individuals' actual perceived value of receiving GS results.