Article

Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.

Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Carcinogenesis (impact factor: 5.7). 03/2006; 27(3):560-7. DOI:10.1093/carcin/bgi232 pp.560-7
Source: PubMed

ABSTRACT Lung cancer is a leading cause of cancer mortality with an inter-individual difference in susceptibility to the disease. The inheritance of low-efficiency genotypes involved in DNA repair and replication may contribute to the difference in susceptibility. We investigated 44 single nucleotide polymorphisms (SNPs) in 20 DNA repair genes including nucleotide excision repair (NER) genes XPA, ERCC1, ERCC2/XPD, ERCC4/XPF and ERCC5/XPG; base excision repair (BER) genes APE1/APEX, OGG1, MPG, XRCC1, PCNA, POLB, POLiota, LIG3 and EXO1; double-strand break repair (DSB-R) genes XRCC2, XRCC3, XRCC9, NBS1 and ATR; and direct damage reversal (DR) gene MGMT/AGT. The study included 343 non-small cell lung cancer (NSCLC) cases and 413 controls from Norwegian general population. Our results indicate that SNPs in the NER genes ERCC1 (Asn118Asn, 15310G>C, 8902G>T), XPA (-4G>A), ERCC2/XPD (Lys751Gln) and ERCC5/XPD (His46His); the BER genes APE1/APEX (Ile64Val), OGG1 (Ser326Cys), PCNA (1876A>G) and XRCC1 (Arg194Trp, Arg280His, Arg399Gln); and the DSB-R genes ATR (Thr211Met), NBS1 (Glu185Gln), XRCC2 (Arg188His) and XRCC9 (Thr297Ile) modulate NSCLC risk. The level of polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adducts in normal lung tissue from 211 patients was analysed. The variant alleles of XRCC1(Arg280His), XRCC1 (Arg399Gln), ERCC1(G8092T), ERCC5(His46His) and MGMT/AGT(Lys178Arg) were more frequent in patients with PAH-DNA adduct levels lower than the mean whereas the XRCC1(Arg194Trp) variant was more frequent in cases with higher adduct levels than the mean.

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Keywords

343 non-small cell lung cancer
 
44 single nucleotide polymorphisms
 
cancer mortality
 
direct damage reversal
 
double-strand break
 
higher adduct levels
 
inter-individual difference
 
leading cause
 
low-efficiency genotypes
 
Lung cancer
 
NBS1
 
NER genes ERCC1
 
normal lung tissue
 
Norwegian general population
 
PAH-DNA
 
PAH-DNA adduct levels lower
 
POLiota
 
polycyclic aromatic hydrocarbon-DNA
 
XRCC2
 
XRCC3