Polymorphisms of DNA repair genes and risk of non-small cell lung cancer (original) (raw)
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* To whom correspondence should be addressed at: Department of Toxicology, National Institute of Occupational Health, P.B. 8149 Dep., N-0033 Oslo, Norway Email: age.haugen@stami.no
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Revision received:
17 September 2005
Accepted:
20 September 2005
Published:
29 September 2005
Cite
Shanbeh Zienolddiny, Daniele Campa, Helge Lind, David Ryberg, Vidar Skaug, Lodve Stangeland, David H. Phillips, Federico Canzian, Aage Haugen, Polymorphisms of DNA repair genes and risk of non-small cell lung cancer, Carcinogenesis, Volume 27, Issue 3, March 2006, Pages 560–567, https://doi.org/10.1093/carcin/bgi232
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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 , POLι , 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.
AP-site, apurinic/apyrymidinic site, APE1, AP-endonuclease-1, APEX, arrayed primer extension, AT, ataxia telangiectasia, ATM, ataxia telangiectasia-mutated, ATR, ATM- and Rad3-related, BER, base excision repair, CYP450, cytochrome P450, DSB-R, double-strand break repair, DR, direct damage reversal, ERCC, excision repair cross complementing, EXO1, exonuclease-1, LIG3, ligase-3, MPG, methylpurine glycosylase, NBS, nijmegen breakage syndrome, NER, nucleotide excision repair, NSCLC, non-small cell lung cancer, O 6 -meG, O 6 -Methylguanine , OGG1, 8-oxo-guanine glycosylase-1, 8-ox-G, 7,8-dihydro-8-oxoguanine, PAH, polycyclic aromatic hydrocarbon, PCNA, proliferating cell nuclear antigen, POLB, polymerase B, SNP, single nucleotide polymorphism, XP, xeroderma pigmentosum, XRCC, X-ray repair cross complementing
Carcinogenesis vol.27 no.3 © Oxford University Press 2005; all rights reserved.
Topic:
- alleles
- polymorphism
- non-small-cell lung carcinoma
- dna
- dna adducts
- dna repair
- genes
- genotype
- o(6)-methylguanine-dna methyltransferase
- single nucleotide polymorphism
- proliferating cell nuclear antigen
- lung cancer
- lung parenchyma
- dna repair gene
- nucleotide excision repair
- base excision repair
- ercc1 gene
- ercc2 gene
- xrcc1 gene
- double-stranded dna breaks
- xpa gene
- norwegian
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