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

Nature. 1998 May 21;393(6682):229-34. doi: 10.1038/30400.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Arginine / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / virology
  • DNA-Binding Proteins*
  • Disease Susceptibility
  • Female
  • Gene Deletion
  • Genotype
  • Heterozygote
  • Humans
  • Oncogene Proteins, Viral / metabolism
  • Papillomaviridae / physiology*
  • Papillomavirus Infections / genetics*
  • Polymorphism, Genetic*
  • Repressor Proteins*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / virology
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Virus Infections / genetics*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / virology


  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • Arginine