Codon 72 polymorphism of p53 as a risk factor for patients with human papillomavirus-associated squamous intraepithelial lesions and invasive cancer of the uterine cervix

Squamous intraepithelial lesions (SIL) and invasive cancer of the uterine c ervix are thought to be a series of lesions derived from normal cervical sq uamous tissue. Infection by high risk human papillomavirus (HPV) and integr ation of viral DNA may initially lead normal cervical cells to become pre-m alignant cells in SIL and result in cervical malignancies later on, High ri sk HPVs, including types 16 and 18, produce a viral protein, E6, which is r equired for viral replication in host cells, The E6 protein is able to bind to host p53 causing inactivation of its function through the mechanism of ubiquitin-dependent degradation. It has recently been reported that the ext ent of p53 dysfunction caused by HPVs depends on the status of a polymorphi sm at codon 72 of p53, Pro or Arg, In that study, it was demonstrated that a patient homozygous for the Arg allele had about a seven times higher risk of developing cervical cancer than a patient homozygous for Pro. In an att empt to confirm this result and elucidate whether this allelic deviation of the Arg genotype seen in invasive cervical cancer occurs in the pre-malign ant lesion SIL, we analyzed 219 SIL and 101 invasive cancer samples from Ja panese patients using a PCR-based assay. Samples from 88 SIL and 76 invasiv e cancers were identified as HPV-infected samples and used for further anal yses, In these, the frequencies of Arg homozygotes were 31.8, 33.0 and 36.8 % in controls, SIL and invasive cancer, respectively. The distributions of the different alleles of codon 72 (Pro/Pro, Pro/Arg and Arg/Arg) did not sh ow significant differences between either control and SIL groups or control and invasive cancer groups. Also, no difference in the frequency of Arg/Ar g genotype was detected even between the control and HSIL groups or control and invasive cancer infected with high risk HPVs groups, In conclusion, th ere was no obvious relationship between the Arg genotype at codon 72 of p53 and predisposition to HPV-associated cervical neoplasia.