ROLE OF A P53 POLYMORPHISM IN THE DEVELOPMENT OF HUMAN PAPILLOMAVIRUS-ASSOCIATED CANCER

The E6 oncoprotein derived from tumour-associated human papillomavirus es (HPVs) binds to and induces the degradation of the cellular tumour- suppressor protein p53. A common polymorphism that occurs in the p53 a mino-acid sequence results In the presence of either a proline or an a rginine at position 72, The effect of this polymorphism on the suscept ibility of p53 to EG-mediated degradation has been Investigated and th e 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 homozygo us arginine-72 p53 compared with the normal population, which indicate d that individuals homozygous for arginine 72 are about seven times mo re susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk fact or in the development of HPV-associated cancers.