p53 and Genetic Susceptibility to Cervical Cancer

In a recent report, Storey et al. ( 1 ) provide compelling experimental evidence that two common polymorphic variants of the p53 tumor suppressor protein differ in their susceptibility to degradation mediated by the E6 oncoprotein of human papillomavirus (HPV). Specifically, the p53 protein with arginine at codon 72 was shown to be more susceptible to E6-induced degradation in vivo than p53 with proline at codon 72. Remarkably, homozygosity for the allele encoding arginine was found at a significantly higher frequency in the germlines of individuals affected by either of two HPV-associated cancers, squamous carcinoma of the cervix or cutaneous carcinomas in renal transplant recipients, than in the germlines of a control population. Storey et al. conclude that individuals homozygous for the arginine-encoding allele of p53 are seven times more susceptible to HPV-associated cervical tumorigenesis than heterozygotes. Squamous carcinoma of the uterine cervix is the most common gynecologic cancer encountered worldwide ( 2 ), and these data provide the first evidence for a possible genetic susceptibility to this malignancy. Furthermore, given that many sexually active females are transiently infected with HPV ( 3 ) and that virtually all squamous carcinomas of the cervix are associated with HPV infection ( 4 ), the public health implications of this finding are potentially enormous.