The p53 codon 72 polymorphism and risk of high-grade cervical intraepithelial neoplasia

Background: The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated in increasing susceptibility of the cervix to human papillomavirus (HPV) infection and thus altering cancer risk. However, research on this topic has been contentious, which prompted us to carry out a case-control study in the Montreal area. Methods: Cases were women with histologically-confirmed high-grade cervical intraepithelial neoplasia (HGCIN). Controls were women without a history of cervical abnormalities. From each woman, we obtained a cervical specimen for HPV testing and p53 genotyping, and a questionnaire was completed. DNA sequencing was used to minimize genotype misclassification. A subsample of specimens was also genotyped using the TaqMan assay. Results: There were 357 cases and 760 controls recruited between February 2001 and December 2003. The distribution of Arg/Arg, Arg/Pro and Pro/Pro was 55.2, 36.4 and 8.4%, respectively, among cases, and 52.1, 38.7 and 9.2%, among controls, corresponding to an odds ratio (OR) adjusted for ancestral origin of 1.16 (95% confidence interval (CI): 0.9-1.5) for Arg/Arg versus other genotypes. When restricted to high-risk HPV-positive women, the adjusted ORs were 1.40 (CI: 0.9-2.1) and 2.12 (CI: 1.1-4.2), for Arg/Arg versus other genotypes and versus Pro/Pro, respectively. The findings were comparable with analyses of genotype results that agreed between DNA sequencing and TaqMan. Conclusions: In this study, we attempted to minimize selection bias, population stratification and genotype misclassification. The results suggest that the role of the p53 codon 72 polymorphism on HGCIN is weak at best. Further research may reveal if the polymorphism has a stronger influence on the risk of invasive cervical cancer.