Influence of common XPD and XRCC1 variant alleles on p53 mutations in lung tumors

被引:31
作者
Hou, SM [1 ]
Ryk, C
Kannio, A
Angelini, S
Fält, S
Nyberg, F
Husgafvel-Pursiainen, K
机构
[1] Karolinska Inst, Dept Biosci Novum, S-14157 Huddinge, Sweden
[2] Finnish Inst Occupat, Lab Mol & Cellular Toxicol, Helsinki, Finland
[3] Karolinska Inst, Inst Environm Med, Div Environm Epidemiol, Stockholm, Sweden
关键词
nucleotide excision repair; XPD genotype; p53; mutation; lung cancer;
D O I
10.1002/em.10128
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
The DNA repair proteins XPD and XRCCl are involved in the nuclectide and base excision repair of DNA lesions induced by many tobacco and environmental carcinogens. Common variant alleles at the XPD (312Asn, 751Gln) and XRCCl (399Gln) loci have been identified and associated with increased risk for lung cancer. We therefore investigated a possible effect of these variant alleles on the frequency and spectrum of p53 mutations in the tumors of 97 Swedish lung cancer patients (56 never-smokers and 41 age-, gender-, and hospital-matched ever-smokers). The p53 gene was mutated in 4 never-smokers (7%) and 11 ever-smokers (27%). Smoking-related transversion-type mutations predominated over transitions among smokers (8:3), but not among never-smokers (1:3). None of the variant alleles altered the overall frequency of p53 mutation. Transversions, however, were marginally increased among patients with at least one XPD variant allele compared with patients who were wild-type homozygotes (73% vs. 25% for the Asp312Asn polymorphism, P 0.095; 78% vs. 33% for Lys751 Gln, P = 0.085). Five of six women or six of seven smokers who carried at least one XPD 751Gln allele had p53 transversion. The XRCCl variant allele did not show any effect on the p53 mutation. We conclude that the XPD variant alleles may be associated with an increased frequency of smoking-related p53 mutations in lung tumors, presumably due to reduced DNA repair proficiency. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:37 / 42
页数:6
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