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


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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This research was funded by grants from the Cancer Research Campaign. Jillian M Birch is Cancer Research Campaign Professorial Research Fellow in Paediatric Oncology and Osborn B Eden is Cancer Research Campaign Professor of Paediatric Oncology at the University of Manchester. We thank the families who took part in the study and the medical personnel who provided clinical details. We are particularly grateful to the many pathologists who supplied material for analysis and to the Office for National Statistics in London for cancer registration data.

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Birch, J., Alston, R., McNally, R. et al. Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20, 4621–4628 (2001).

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  • germline TP53 mutations
  • cancer frequency
  • cancer predisposition

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