The Swedish p53 Study (SWEP53) is a germ line TP53 pathogenic variant patient registry with three optional parts: a biobank, a surveillance program and a psychosocial evaluation of the surveillance. The full study outline was published in the journal Hereditary Cancer in Clinical Practice.
Tumor protein p53 encoded by the gene TP53 is known as the “guardian of the genome” due to its role in the surveillance of DNA damage, DNA repair and programmed cell death. It plays a prominent role in the prevention of age-related diseases such as cancer in people. An interesting observation in African elephants illustrates the importance of p53 for cancer prevention.
African elephants have 19 extra copies of TP53 known as retrogenes, 14 of which express truncated p53 proteins. As a result, elephant cells undergo programmed cell death, in response to DNA damage, much more readily than human cells. Only 3% of tracked elephants die of cancer, compared with 28% of all people in economically advanced countries, despite being 66x heavier than people.
The extra p53 retrogenes may also be functionally redundant, compensating for any somatic, and perhaps also germline, loss of TP53 due to mutation. Data from the 1000 genomes project indicates that the worldwide prevalence of germline pathogenic TP53 variants that predispose people to cancer is between 1:5,000–1:20,000 individuals.
The estimated lifetime risk of cancer for these individuals is between 73-100%. In Sweden the current guidelines for people with a clinically actionable (pathogenic or likely pathogenic) germline TP53 variants advises patients to take part in the Swedish P53 Study (SWEP53).
The consented study consists of four parts, three of which are optional:
- A national registry containing genetic data, cancer history and family history. The registry includes both adults and children.
- Surveillance in the form of a standardized annual general physical examination with whole-body MRI. Women undergo yearly breast-MRI and breast ultrasound, as applicable. Those up to 15 years old will be offered abdominal ultrasound, urine corticosteroid profile and a tri-monthly paediatrician consult. Ages 15–18 may take part in the MRI monitoring or continue within the childhood protocol.
- A biobank at the Karolinska University Laboratory of DNA and plasma from peripheral blood. If a participant develops cancer, fibroblasts from cultured skin biopsies and DNA from tumour samples are collected. Circulating tumour cells are stored, if feasible. As a complement to MRI, cell free DNA from plasma will be analysed using tumour DNA as a reference.
- Adult patient reported outcomes will be assessed concerning health related quality of life including possible environmental modifying factors.
The surveillance within the SWEP53 study is intended to proceed for five years, and remain open for new participants until 2026.
Underlining the importance of the study the authors write, “There is no national registry containing information on all known TP53 carriers and thus the incidence in Sweden is unknown. Only 25 adult carriers are known in the Stockholm area, much less than the expected 100–400 based on the supposed incidence 1:5000–1:20000, suggesting a huge under-diagnosis of this condition.”