Preferences to receive unsolicited findings of germline genome sequencing in a large population of patients with cancer

Abstract

BackgroundIn precision medicine, somatic and germline DNA sequencing are essential to make genome-guided treatment decisions in patients with cancer. However, it can also uncover unsolicited findings (UFs) in germline DNA that could have a substantial impact on the lives of patients and their relatives. It is therefore critical to understand the preferences of patients with cancer concerning UFs derived from whole-exome (WES) or whole-genome sequencing (WGS).MethodsIn a quantitative multicentre study, adult patients with cancer (any stage and origin of disease) were surveyed through a digital questionnaire based on previous semi-structured interviews. Background knowledge was provided by showing two videos, introducing basic concepts of genetics and general information about different categories of UFs (actionable, non-actionable, reproductive significance, unknown significance).ResultsIn total 1072 patients were included of whom 701 participants completed the whole questionnaire. Overall, 686 (85.1%) participants wanted to be informed about UFs in general. After introduction of four UFs categories, 113 participants (14.8%) changed their answer: 718 (94.2%) participants opted for actionable variants, 537 (72.4%) for non-actionable variants, 635 (87.0%) participants for UFs of reproductive significance and 521 (71.8%) for UFs of unknown significance. Men were more interested in receiving certain UFs than women: non-actionable: OR 3.32; 95% CI 2.05 to 5.37, reproductive significance: OR 1.97; 95% CI 1.05 to 3.67 and unknown significance: OR 2.00; 95% CI 1.25 to 3.21. In total, 244 (33%) participants conceded family members to have access to their UFs while still alive. 603 (82%) participants agreed to information being shared with relatives, after they would pass away.ConclusionOur study showed that the vast majority of patients with cancer desires to receive all UFs of genome testing, although a substantial minority does not wish to receive non-actionable findings. Incorporation of categories in informed consent procedures supports patients in making informed decisions on UFs.

Assigning evidence to actionability: An introduction to variant interpretation in precision cancer medicine

“…A significant fraction (9%-12%) of cancer patients carries a germline mutation predisposing for different hereditary cancer syndromes [24][25][26] and a majority of patients expresses a clear preference to be informed about the results of germline analyses. 27 It is thus necessary to consider possible germline involvement of (likely) pathogenic variants that may cause cancer predisposition, both with regard to therapy as well as to preventive measures for the patient and affected family members. 24,28 Somatic and germline variants cannot be discriminated by Variant interpretation in a germline context should be performed in accordance with published guidelines, such as the American College of Medical Genetics and Genomics (ACMG) criteria for germline variant interpretation.…”

“…A significant fraction (9%–12%) of cancer patients carries a germline mutation predisposing for different hereditary cancer syndromes 24‐26 and a majority of patients expresses a clear preference to be informed about the results of germline analyses 27 . It is thus necessary to consider possible germline involvement of (likely) pathogenic variants that may cause cancer predisposition, both with regard to therapy as well as to preventive measures for the patient and affected family members 24,28 .…”

Participant Choice towards Receiving Potential Additional Findings in an Australian Nephrology Research Genomics Study

“…Attitudes ranged from wanting to obtain all information about health risks to; alleviate uncertainty, provision of familial information, engage in preventative measures, and ensure quality of life, to not wanting to receive extra findings due to; religious or personal beliefs, burden of information, anxiety and worry or concerns. These findings in regard to disclosure of potential AFs are further validated by larger scale diagnostic genomic studies in both general [ 9 ] and cancer genetics [ 10 ] settings. The diverse set of views shows the importance of patient choice to be a core genomic consent component of the patient clinician interaction for clinical genomic sequencing [ 8 ].…”

Study protocol of the GLOW study: maximising treatment options for recurrent glioblastoma patients by whole genome sequencing-based diagnostics—a prospective multicenter cohort study

“…Participants can limit this choice to disease that are preventable or treatable and can provide their preference for family to obtain access to heritable information after being deceased. This germline consenting model is optimized based on patient preferences [ 24 ] and also was applied in the CPCT-02 (open, NCT01855477), WIDE (closed) [ 25 ] and DRUP (open, NCT02925234) studies. All adverse events (AEs) reported spontaneously by the subject or observed by the investigator or his staff will be recorded.…”