XRCC1 polymorphism and lung cancer risk

Abstract

DNA repair plays a critical role in protecting the genome of the cell from the insults of carcinogens or ionizing radiation. Reduced DNA repair capacity can increase the susceptibility to environmental- or occupational-induced cancers. Three coding polymorphisms at codon 194, codon 280 and codon 399 in the x-ray cross complementing group 1 (XRCC1) DNA repair gene have been identified, and it is possible that these polymorphisms may affect DNA repair capacity and thus modulate cancer susceptibility. In this review, we summarize the literature and discuss the relevance of XRCC1 polymorphisms and lung cancer risk. The frequency of genetic polymorphisms is dependent on the ethnic origins of a population. The frequency of the variant allele of codon 194 among Asians is on average 31.2% (95% confidence interval [CI]: 29.6-32.8), which is significantly higher than among Caucasians (6.6%; 95% CI: 5.9-7.4) or Africans (7.3%; 95% CI: 5.7-9.2). The variant allele in codon 399 occurs among Africans at a frequency of 15.5% (95% CI: 13.5-17.7), 34.7% in Caucasians (95% CI: 33.8-35.6) and 26.5% in Asians (95% CI: 25.6-27.4). Results regarding lung cancer risk are inconsistent. The lung cancer risk associated with polymorphisms of the XRCC1 codon 194 demonstrate an odds ratio (OR) of around 1.0. For the XRCC1 codon 280, lung cancer risk varied between ORs of 0.26 and 1.8; and for the XRCC1 codon 399 between 0.32 and 3.25. Only two studies showed significantly elevated risks (OR: 3.25; 95% CI: 1.2-10.7; OR: 1.3; 95% CI: 1.0-1.8, respectively), whereas one study showed a decreased lung cancer risk (OR: 0.60; 95% CI: 0.46-40.80). Lung cancer risk increased with cigarette smoking. A significant association was not observed between the single-nucleotide polymorphisms and tobacco-related cancers. Lung cancer risk increased significantly for the variant XRCC1 -77 genotypes (TC and CC) compared with the TT genotype (OR: 1.46; 95% CI: 1.18-1.82). The risk was more pronounced in smokers (OR: 1.63; 95% CI: 1.20-2.21) than in nonsmokers (OR: 1.28; 95% CI: 0.94-1.76). No association with polymorphisms were found for various histological tumor types. The XRCC1 399 Gln/Gln variant genotype was associated with a higher median survival time.