P53 codon 72 polymorphism and susceptibility to development of human papilloma virus-associated cervical cancer in Indian women.

Abstract

Infection with human papilloma virus (HPV) is an important etiological factor in the development of cervical cancer and it has been proposed that individuals homozygous for Arg/Arg at codon-72 of p53 are seven times more susceptible to HPV-mediated cancer. In this study, we have analyzed the genetic predisposition of the India population to HPV infection and cervical carcinogenesis. We investigated 71 cases of squamous cell carcinoma of the cervix, 14 cases of low-grade squamous intraepithelial lesions, 25 cases of high-grade squamous intraepithelial lesions and 29 noncancer controls for presence of HPV16/18 infections by L-1-specific PCR assay and Southern hybridization, and its association with polymorphism at p53 codon 72. We observed that 69.1% (76/110) of the cervical cancer patients were HPV positive, among which the presence of HPV16, 18 and 16/18 coinfection was 40.9%, 8.2% and 13.6%, respectively. The allele frequencies of the three p53 genotypes Arg/Arg, Arg/Pro and Pro/Pro in the HPV-positive tumour samples were 0.34, 0.57 and 0.09 in comparison with frequencies of 0.18, 0.44 and 0.38 for HPV-negative tumours. Hence, there is a significant difference in the allelic frequency of p53 Arg/Arg in high-risk HPV-infected cervical carcinoma cases (0.34) and HPV-negative carcinomas (0.18). Our results indicate a striking over-representation of homozygous arginine at codon 72 of p53 in HPV-associated cervical carcinogenesis. We conclude that women with Arg/Arg homozygous allele are more prone to infection by HPV16/18, which leads to cervical carcinomas having poor prognosis.