Influence of polymorphism in DNA repair and defence genes on p53 mutations in bladder tumours.
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.
Ryk
Charlotta
C
Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden. charlotta.ryk@biosci.ki.se
Kumar
Rajiv
R
Sanyal
Somali
S
de Verdier
Petra J Berggren
PJ
Hemminki
Kari
K
Larsson
Per
P
Steineck
Gunnar
G
Hou
Sai-Mei
SM
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*