Attitudes to genetic information in Li-Fraumeni families (and their physicians) and the consequences of cancer screening in these families

Abstract

Individuals with germline TP53 gene mutations have the Li-Fraumeni Syndrome (LFS). The aim of this thesis was to examine the attitudes to genetic information in TP53 families and their physicians, and the consequences of cancer screening in these families. To do this, this thesis addressed three aims using a mixed methods approach. Factors contributing to low levels of genetic testing for germline TP53 mutations were explored through a qualitative grounded theory study, which examined the impact of recent genetic information from the perspective of sarcoma patients (and their families) with newly research-identified germline TP53 mutations. The results showed sarcoma patients and their families might not act on knowledge of their TP53 mutation status. Timing and context of notification of genetic results appeared to motivate people to act on the information. Second, possible clinician barriers to genetic testing for TP53 mutations in sarcoma patients were explored through an international cross sectional survey. Results from this survey suggest improved education of oncologists may overcome one obstacle to testing for germline TP53 mutations in patients with sarcoma. Once sarcoma patients know that they are carrying a germline TP53 mutation, likely they will be aware of their high risk of developing second primary malignancies. This may prompt them to explore cancer surveillance strategies despite a current lack of proven benefit. Whole body MRI is a new low risk cancer screening technology now used in some TP53 germline mutation carriers. The third study in this thesis used longitudinal mixed methods to investigate the psychosocial impact of annual whole-body MRI cancer screening. Cancer screening does not appear to have a negative psychosocial impact, and seems to aid coping in the face of a germline TP53 mutation. If these trends are sustained over time some morbidity associated with having a TP53 gene mutation may be ameliorated. Overall, the findings of this thesis will inform the care of patients with sarcoma by increasing access to clinical genetic testing, and optimising the clinical care pathway if a TP53 mutation has been identified.