Preferences to Receive Unsolicited Findings of Germline Genome Sequencing in a Large Population of Cancer Patients

Abstract

Background: In precision medicine, somatic and germline DNA sequencing are essential to make genome-guided treatment decisions in cancer patients. 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 cancer patients' preferences concerning UFs derived from whole-exome (WES) or whole-genome sequencing (WGS). Methods: In a quantitative multi-center study, adult cancer patients (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). Findings: In 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 - 5.37, reproductive significance: OR 1.97; 95% CI 1.05 - 3.67 and unknown significance: OR 2.00; 95% CI 1.25 - 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. Interpretation: Our study showed that the vast majority of cancer patients 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. Funding Statement: This work was supported by the Dutch Cancer Foundation (KWF) [grant UU2014-7469]. Declaration of Interests: The authors have declared no conflicts of interest. Ethics Approval Statement: The research protocol was approved by the Research Ethics Committee of the University Medical Center Utrecht (The Netherlands), and informed consent was obtained from all participants