Relative frequency and morphology of cancers in carriers of germline TP53 mutations
Open accessAbstract
The spectrum and frequency of cancers associated with germline TP53 mutations are uncertain. To address this issue a cohort of individuals from 28 families with Li-Fraumeni syndrome, segregating germline TP53 mutations was established. Predicted cancers were estimated by applying age, morphology, site and sex-specific UK cancer statistics to person-years at risk. Observed and predicted cancers were compared and two-sided P-values calculated. Cancer types occurring to excess and showing P-values <0.02, were designated strongly associated with germline TP53 mutations. These were removed from the data and a second round of analyses performed. Cancer types with P-values <0.02 and 0.02-0.05 in the second round analyses were considered moderately and weakly associated respectively. Strongly associated cancers were: breast carcinoma, soft tissue sarcomas, osteosarcoma, brain tumours, adrenocortical carcinoma, Wilms' tumour and phyllodes tumour. Carcinoma of pancreas was moderately associated. Leukaemia and neuroblastoma were weakly associated. Other common carcinomas including lung, colon, bladder, prostate, cervix and ovary did not occur to excess. Although breast carcinoma and sarcomas were numerically most frequent, the greatest increases relative to general population rates were in adrenocortical carcinoma and phyllodes tumour. We conclude that germline TP53 mutations do not simply increase general cancer risk. There are tissue-specific effects.
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Only a minority of patients with Li Fraumeni syndrome, most of whom harbor germline heterozygous TP53 mutations, develop AML or MDS.
“Consistent with this observation, only a minority of patients with Li Fraumeni syndrome, most of whom harbor germline heterozygous TP53 mutations, develop AML or MDS 23.”
From Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia (2015) · cites this paper as [23]
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- Authors
- Birch, J. M., Alston, R. D., McNally, R. J., Evans, D. G. R., Kelsey, A. M., Harris, M., Eden, O. B., & Varley, J. M.
- Affiliations
- Royal Manchester Children's Hospital (GB)
- St Mary's Hospital (GB)
- Cancer Research UK Manchester Institute (GB)
- Corresponding author
- Birch, Jillian M
- Venue
- Oncogene
- Published
- 2001-08-02
- Volume
- 20
- Issue
- 34
- Pages
- 4621-4628
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2051972371
- Cited by
- 467
- References
- 39
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 16 · 2023: 13 · 2022: 14 · 2021: 26 · 2020: 23 · 2019: 13 · 2018: 12 · 2017: 17 · 2016: 26 · 2015: 27 · 2014: 27 · 2013: 25 · 2012: 24
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Keywords
- germline TP53 mutation, Li-Fraumeni syndrome, cancer spectrum, cancer risk, breast cancer, soft tissue sarcoma, osteosarcoma, brain tumors, adrenocortical carcinoma, phyllodes tumor, leukemia, neuroblastoma
- MeSH terms
- Adolescent, Adult, Aged, Child, Child, Preschool, Family Health, Female, Heterozygote, Humans, Infant, Male, Middle Aged, Cohort Studies, Tumor Suppressor Protein p53, Li-Fraumeni Syndrome, Germ-Line Mutation, Genetic Predisposition to Disease
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