title: Influence of polymorphism in DNA repair and defence genes on p53 mutations in bladder tumours.
abstract: We studied the effects of polymorphisms in nine genes involved in DNA repair and detoxification on occurrence and type of p53 mutation in 327 bladder cancer patients. The included polymorphisms are XPC(Lys939Gln), XPD(Lys751Gln), XPG(Asp1104His), XRCC1(Arg3999Gln), XRCC3(Thr241Met), NBS1(Glu185Gln), cyclin D1(Pro241Pro), MTHFR(Ala222Val and Glu429Ala) and NQO1(Arg139Trp and Pro187Ser). We found increased risk for p53 mutation among cyclin D1 variant allele homozygotes (OR 2.4 CI 0.8-6.7). Among non-smokers, 75% (3/4) with p53 mutation but only 12.5% (3/24) without p53 mutations were XRCC3 241Met homozygotes (P=0.03). Among smokers, all p53 transversions (3/3), but only 41.7% (5/12) of p53 transitions were found among carriers of the XPC 939Gln allele. Individuals carrying the NQO1 187Ser allele showed increased risk for p53 transversions (OR 4.7, CI 0.9-26.1). All (2/2) NQO1 139Trp allele carriers but only 17.5% (7/40) of the Arg139 homozygotes had p53 transversions. Our findings suggest that altered repair and detoxification due to genetic polymorphism may influence the occurrence of p53 mutations in bladder cancer.
authors.affiliation: Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden. charlotta.ryk@biosci.ki.se
authors.forename: Charlotta
authors.initials: C
authors.lastname: Ryk
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Somali
authors.initials: S
authors.lastname: Sanyal
authors.forename: Petra J Berggren
authors.initials: PJ
authors.lastname: de Verdier
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Per
authors.initials: P
authors.lastname: Larsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Steineck
authors.forename: Sai-Mei
authors.initials: SM
authors.lastname: Hou
mesh_terms: D004260:DNA Repair / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D001749:Urinary Bladder Neoplasms / Q000235:genetics*