title: P53 codon 72 (Arg72Pro) polymorphism and prostate cancer risk: association between disease onset and proline genotype.
abstract: The tumor suppressor gene p53 plays an important role in the stress response of the cell and is mutated in 50% of all human tumors. The p53 Arg72Pro single-nucleotide polymorphism (SNP) was found to be associated with an increased risk of various malignancies. Biochemical and biological differences between the 2 polymorphic variants of wild-type P53 might lead to distinct susceptibility to HPV- and non-HPV-induced tumors. For prostate cancer, only limited data are available, especially in the Caucasian population. Therefore, we determined the distribution of the Arg72Pro SNP in a Caucasian case-control study including 118 prostate cancer patients and 194 male controls without any malignancy using restriction fragment length polymorphism analysis. A subset of 33 tumors was tested for HPV infection, and no HPV DNA was found. Cases and controls showed similar distributions of alleles in the SNP (p = 0.720). Regarding the onset of the disease, patients diagnosed at ≤60 years of age and older patients (>60 years of age) showed a significant difference in genotype distribution (p = 0.035); there was also an increased occurrence of risk allele Pro72 in cases aged ≤60 years (p = 0.045). A subset of 64 prostate tumors was stained immunohistochemically for P53. 5 of 64 prostate tumors (7.8%) were positive for P53 expression, indicating integrity of the protein in the majority of cases. Genotype distribution showed no association with the Gleason score or additional histopathological characteristics. This study shows that the overall risk of prostate cancer was not associated with Arg72Pro SNP and HPV infection in our cohort. However, disease onset might be modulated by the p53 Pro72 allele, suggesting an important role of apoptosis regulation in prostate carcinogenesis.
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rogler
authors.forename: Michael
authors.initials: M
authors.lastname: Rogenhofer
authors.forename: Albert
authors.initials: A
authors.lastname: Borchardt
authors.forename: Jens-Claudio
authors.initials: JC
authors.lastname: Lunz
authors.forename: Antje
authors.initials: A
authors.lastname: Knoell
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.forename: Wolf
authors.initials: W
authors.lastname: Wieland
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D016022:Case-Control Studies; D005787:Gene Frequency; D016158:Genes, p53; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53