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

Author

Listed:
  • Alan Storey

    (Imperial Cancer Research Fund, Skin Tumour Laboratory)

  • Miranda Thomas

    (International Centre for Genetic Engineering and Biotechnology)

  • Ann Kalita

    (International Centre for Genetic Engineering and Biotechnology)

  • Catherine Harwood

    (Imperial Cancer Research Fund, Skin Tumour Laboratory)

  • Daniela Gardiol

    (International Centre for Genetic Engineering and Biotechnology)

  • Fiamma Mantovani

    (International Centre for Genetic Engineering and Biotechnology)

  • Judith Breuer

    (St Bartholomews and The Royal London Hospital School of Medicine and Dentistry, Queen Mary and Westfield College)

  • Irene M. Leigh

    (Imperial Cancer Research Fund, Skin Tumour Laboratory)

  • Greg Matlashewski

    (Institute of Parasitology and McGill Cancer Centre, McGill University, Macdonald Campus)

  • Lawrence Banks

    (Institute of Parasitology and McGill Cancer Centre, McGill University, Macdonald Campus)

Abstract

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.

Suggested Citation

  • Alan Storey & Miranda Thomas & Ann Kalita & Catherine Harwood & Daniela Gardiol & Fiamma Mantovani & Judith Breuer & Irene M. Leigh & Greg Matlashewski & Lawrence Banks, 1998. "Role of a p53 polymorphism in the development of human papilloma-virus-associated cancer," Nature, Nature, vol. 393(6682), pages 229-234, May.
    • Handle: RePEc:nat:nature:v:393:y:1998:i:6682:d:10.1038_30400
    DOI: 10.1038/30400
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