title: p53 codon 72 polymorphic variants, loss of allele-specific transcription, and human papilloma virus 16 and/or 18 E6 messenger RNA expression in squamous cell carcinomas of the head and neck.
abstract: A polymorphism at codon 72 of the human tumor suppressor p53 determines translation into either arginine or proline. Yet, the impact of this amino acid variability on the risk to develop malignant tumors, particularly carcinomas associated with human papilloma virus (HPV) infections, remains unresolved because of contradictory results. To address a potential correlation between the different genotypes and the manifestation of squamous cell carcinomas of the head and neck (SCCHN), we determined the p53 codon 72 in 193 healthy subjects and 122 unselected SCCHN with known HPV status. Furthermore, loss of allele-specific transcription was analyzed in p53 codon 72 heterozygous (Arg/Pro) SCCHN and correlated with HPV 16 and/or 18 E6 transcript expression. We found a moderately increased risk (odds ratio, 1.86; 95% confidence interval, 1.0-3.3) for individuals with germ line heterozygosity to develop SCC of the pharynx. On the other hand, p53 codon 72 polymorphic variants, most notably the Arg/Arg genotype, showed no association with the presence of HPV 16 and/or 18 E6 transcript. Moreover, there was no evidence for HPV-driven selection in SCCHN with allele-specific loss of transcription. Our data suggest that the p53 codon 72 polymorphism has a minor impact on the development of SCCHN.
authors.affiliation: Department of Otorhinolaryngology/Head & Neck Surgery, Heinrich-Heine-University, Moorenstr. 5, D-40225 Düsseldorf, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Scheckenbach
authors.forename: Oliver
authors.initials: O
authors.lastname: Lieven
authors.forename: Karl
authors.initials: K
authors.lastname: Götte
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bockmühl
authors.forename: Rainer
authors.initials: R
authors.lastname: Zotz
authors.forename: Henning
authors.initials: H
authors.lastname: Bier
authors.forename: Vera
authors.initials: V
authors.lastname: Balz
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000086082:Viroporin Proteins
chemical_list: D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins