Relative frequency and morphology of cancers in carriers of germline TP53 mutations.

2.50
Hdl Handle:
http://hdl.handle.net/10541/84125
Title:
Relative frequency and morphology of cancers in carriers of germline TP53 mutations.
Authors:
Birch, Jillian M; Alston, Robert D; McNally, Richard J Q; Evans, D Gareth R; Kelsey, Anna M; Harris, Martin; Eden, Tim O B; Varley, Jennifer
Abstract:
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.
Affiliation:
CRC Paediatric and Familial Cancer Research Group and Department of Pathology, Royal Manchester Children's Hospital, Stancliffe, Hospital Road, Manchester M27 4HA, UK. Jillian.m.birch@man.ac.uk
Citation:
Relative frequency and morphology of cancers in carriers of germline TP53 mutations. 2001, 20 (34):4621-8 Oncogene
Journal:
Oncogene
Issue Date:
2-Aug-2001
URI:
http://hdl.handle.net/10541/84125
DOI:
10.1038/sj.onc.1204621
PubMed ID:
11498785
Type:
Article
Language:
en
ISSN:
0950-9232
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBirch, Jillian Men
dc.contributor.authorAlston, Robert Den
dc.contributor.authorMcNally, Richard J Qen
dc.contributor.authorEvans, D Gareth Ren
dc.contributor.authorKelsey, Anna Men
dc.contributor.authorHarris, Martinen
dc.contributor.authorEden, Tim O Ben
dc.contributor.authorVarley, Jenniferen
dc.date.accessioned2009-10-13T09:14:44Z-
dc.date.available2009-10-13T09:14:44Z-
dc.date.issued2001-08-02-
dc.identifier.citationRelative frequency and morphology of cancers in carriers of germline TP53 mutations. 2001, 20 (34):4621-8 Oncogeneen
dc.identifier.issn0950-9232-
dc.identifier.pmid11498785-
dc.identifier.doi10.1038/sj.onc.1204621-
dc.identifier.urihttp://hdl.handle.net/10541/84125-
dc.description.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.en
dc.language.isoenen
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshCohort Studies-
dc.subject.meshFamily Health-
dc.subject.meshFemale-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGerm-Line Mutation-
dc.subject.meshHeterozygote-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshLi-Fraumeni Syndrome-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshTumor Suppressor Protein p53-
dc.titleRelative frequency and morphology of cancers in carriers of germline TP53 mutations.en
dc.typeArticleen
dc.contributor.departmentCRC Paediatric and Familial Cancer Research Group and Department of Pathology, Royal Manchester Children's Hospital, Stancliffe, Hospital Road, Manchester M27 4HA, UK. Jillian.m.birch@man.ac.uken
dc.identifier.journalOncogeneen

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