title: Impact of polymorphisms in xeno(endo)biotic metabolism on pattern and frequency of p53 mutations in bladder cancer.
abstract: We have analyzed the tumor biopsies of 45 patients with bladder cancer for p53 mutations by direct sequencing. In addition to N-acetyltransferase-2 (NAT2) and GSTM1 allelisms, which were examined previously, we have analyzed the genetic polymorphisms of GSTT1, GSTP1, COMT, NQO1, TS-SULT and MPO in buffy coat DNA using PCR-based methods. All subjects were interviewed through a questionnaire on smoking, dietary habits and other risk factors. No specific pattern was evident for p53 mutations. Eight out of ten mutations occurred in grade 3 tumors. All p53 mutations occurred in subjects with the COMT mutated allele (p=0.03). The prevalence of cases with p53 mutations was 3.5-fold higher in subjects with wild type than in those with variant GSTP1 alleles (p=0.03). The other polymorphisms investigated were not associated with p53 mutations.
authors.affiliation: Unit of Cancer Epidemiology, Dipartimento di Scienze Biomediche e Oncologia Umana, via Santena 7, 10126, Turin, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Martone
authors.forename: P
authors.initials: P
authors.lastname: Vineis
authors.forename: C
authors.initials: C
authors.lastname: Malaveille
authors.forename: B
authors.initials: B
authors.lastname: Terracini
mesh_terms: D000368:Aged; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016660:NAD(P)H Dehydrogenase (Quinone); D011110:Polymorphism, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D007527:Isoenzymes; D016159:Tumor Suppressor Protein p53; D015262:Xenobiotics; D016660:NAD(P)H Dehydrogenase (Quinone); D002394:Catechol O-Methyltransferase; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase