Abstract 1187: Inactivation of p53 in HPV-infected lung cancer is correlated with p53 codon 72 genotypes and HPV 16/18 E6 protein expression but not with HPV 16/18 DNA

Abstract

Abstract Background. A polymorphism at codon 72 of the p53 tumor suppressor gene is a possible determinant for cancer risk, particularly for carcinomas associated with HPV infection. We recently reported that high-risk HPV 16/18 E6 protein was associated with p53 protein degradation in lung cancer. The present study addressed the relationship between the different p53 genotypes and HPV oncoprotein expression with respect to p53 protein degradation in 319 primary lung cancer patients. Methods. The p53 codon 72 polymorphisms, HPV 16/18 infection, HPV 16/18 E6 and p53 protein expression were determined for all patients by PCR-RFLP, nested-PCR and immunohistochemical analysis. Results. The presence of HPV 16/18 DNA and E6 protein was inversely correlated with p53 expression. The frequency of p53 protein degradation in HPV 16/18 E6-positive/Arg/Arg lung cancer tumours was also much higher than in the HPV 16/18 E6-negative/Arg/Arg, HPV 16/18 E6-positive/Arg/pro+pro/pro, and HPV 16/18 E6-negative/Arg/pro+pro/pro groups. After adjusting for polymorphism, HPV 16/18 E6 protein, HPV 16/18 DNA, gender, smoking habit and tumor type, the major contributors to p53 degradation in lung cancer patients were p53 codon72 polymorphism and HPV 16/18 E6 oncoprotein expression. This correlation was not found for HPV 16/18 DNA infection. Conclusion. These results suggested that the involvement of HPV 16/18 E6 protein in the p53 inactivation that contributes to HPV-infected lung tumourigenesis is correlated with the p53 codon 72 genotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1187. doi:1538-7445.AM2012-1187