Pursuing germline genome sequencing to reduce illness uncertainty may involve additional uncertainties for cancer...

Cancer-related illness uncertainty has been associated with poorer psychological outcomes for patients. While some cancer patients believe obtaining genomic information will reduce their illness uncertainty, the complexity of genomics has the potential to compound illness uncertainty. The aim of this mixed-methods study was to investigate uncertainty in patients with a cancer of likely heritable origin immediately following their decision to have germline genome sequencing. Participant (N = 348) negative attitudes toward uncertainty were associated with higher satisfaction with decision to have germline genome sequencing and greater fear of cancer recurrence. Thematic analysis of semi-structured interviews with a subset of participant (N = 20) revealed the following four themes: (a) germline genome sequencing to reduce illness uncertainty; (b) germline genome sequencing to reduce uncertainty related to relatives' risk; (c) uncertainty generated by germline genome sequencing; and (d) resilience and coping with uncertainty. This study demonstrated the complexity of uncertainty in germline genome sequencing in cancer patients. These results provide genomic healthcare professionals with important information about cancer patient's motivation to pursue germline genome sequencing, the specific uncertainties generated by germline genome sequencing, and how cancer patients cope with uncertainty.