title: 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.
abstract: Squamous intraepithelial lesions (SIL) and invasive cancer of the uterine cervix are thought to be a series of lesions derived from normal cervical squamous tissue. Infection by high risk human papillomavirus (HPV) and integration of viral DNA may initially lead normal cervical cells to become pre-malignant cells in SIL and result in cervical malignancies later on. High risk HPVs, including types 16 and 18, produce a viral protein, E6, which is required 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 extent of p53 dysfunction caused by HPVs depends on the status of a polymorphism 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 attempt to confirm this result and elucidate whether this allelic deviation of the Arg genotype seen in invasive cervical cancer occurs in the pre-malignant lesion SIL, we analyzed 219 SIL and 101 invasive cancer samples from Japanese patients using a PCR-based assay. Samples from 88 SIL and 76 invasive cancers were identified as HPV-infected samples and used for further analyses. 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 show significant differences between either control and SIL groups or control and invasive cancer groups. Also, no difference in the frequency of Arg/Arg genotype was detected even between the control and HSIL groups or control and invasive cancer infected with high risk HPVs groups. In conclusion, there was no obvious relationship between the Arg genotype at codon 72 of p53 and predisposition to HPV-associated cervical neoplasia.
authors.affiliation: Department of Obstetrics and Gynecology, Asahikawa Medical College, Nishikagura 4-5-3-11, Asahikawa 078-8510, Japan. tyamashi@asahikawa-med.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Yaginuma
authors.forename: Y
authors.initials: Y
authors.lastname: Saitoh
authors.forename: K
authors.initials: K
authors.lastname: Kawai
authors.forename: T
authors.initials: T
authors.lastname: Kurakane
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D003062:Codon / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012097:Repressor Proteins; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014412:Tumor Virus Infections / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53