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Role of a p53 polymorphism in the development of human papilloma-virus-associated cancer

Nature volume 393, pages 229234 (21 May 1998) | Download Citation

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The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.

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Acknowledgements

We thank P. Spink for assistance with the development of HPV screening and typing; I. Jacobs and H. Stevens for cervical and normal DNA; D. Pim for comments on the manuscript; and A.Norman for statistical analysis. G.M. acknowledges the support from the National Cancer Institute of Canada with funds from the Canadian Cancer Society and NSERC. C.H. is the recipient of a MRC Clinical Training Fellowship. G.M., A.S. and L.B. thank L. Crawford for insightful discussions.

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Author notes

    • Greg Matlashewski
    •  & Lawrence Banks

    These authors contributed equally to this work

Affiliations

  1. *Imperial Cancer Research Fund, Skin Tumour Laboratory, 2 Newark Street, London E1 2AT, UK

    • Alan Storey
    • , Catherine Harwood
    •  & Irene M. Leigh
  2. †International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy

    • Miranda Thomas
    • , Ann Kalita
    • , Daniela Gardiol
    •  & Fiamma Mantovani
  3. ‡Institute of Parasitology and McGill Cancer Centre, McGill University, Macdonald Campus, 21,111 Lakeshore Road, Ste Anne de Bellevue, Qubc H9X 3V9, Canada

    • Greg Matlashewski
    •  & Lawrence Banks
  4. §Department of Medical Microbiology, St Bartholomews and The Royal London Hospital School of Medicine and Dentistry, Queen Mary and Westfield College, Ashfield Street, London E1 1BB, UK

    • Judith Breuer

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Correspondence to Greg Matlashewski or Lawrence Banks.

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https://doi.org/10.1038/30400

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