Relative frequency and morphology of cancers in carriers of germline TP53 mutations.
AuthorsBirch, Jillian M
Alston, Robert D
McNally, Richard J Q
Evans, D Gareth R
Kelsey, Anna M
Eden, Tim O B
AffiliationCRC Paediatric and Familial Cancer Research Group and Department of Pathology, Royal Manchester Children's Hospital, Stancliffe, Hospital Road, Manchester M27 4HA, UK. Jillian.email@example.com
MetadataShow full item record
AbstractThe 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.
CitationRelative frequency and morphology of cancers in carriers of germline TP53 mutations. 2001, 20 (34):4621-8 Oncogene
- TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes.
- Authors: Ruijs MW, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FB, Kluijt I, Sijmons RH, Aalfs CM, Wagner A, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia EB, Meijers-Heijboer H, Ten Kate LP, Menko FH, van 't Veer LJ
- Issue date: 2010 Jun
- Cancer phenotype correlates with constitutional TP53 genotype in families with the Li-Fraumeni syndrome.
- Authors: Birch JM, Blair V, Kelsey AM, Evans DG, Harris M, Tricker KJ, Varley JM
- Issue date: 1998 Sep 3
- The TP53 mutation, R337H, is associated with Li-Fraumeni and Li-Fraumeni-like syndromes in Brazilian families.
- Authors: Achatz MI, Olivier M, Le Calvez F, Martel-Planche G, Lopes A, Rossi BM, Ashton-Prolla P, Giugliani R, Palmero EI, Vargas FR, Da Rocha JC, Vettore AL, Hainaut P
- Issue date: 2007 Jan 8
- [When is it useful to look for TP53 germline gene mutations in families of oncology patients?].
- Authors: Trková M, Sedlácek Z
- Issue date: 2003
- [Germline mutations of the p53 gene].
- Authors: Frebourg T
- Issue date: 1997 Dec