Using the multifactor dimensionality reduction method, we found a model of gene-gene interactions associated with the risk of lung cancer: NBS1 (rs1805794)-XRCC1 (rs25487)-hOGG1 (rs1052133)-XPG (rs17655).
To analyze the relationship of GSTT1, GSTM1, XRCC1 (rs25487), ERCC1 (rs11615, rs3212986), ERCC2 (rs13181), XRCC3 (rs861539), OGG1 (rs1052133), and Alpha-1-Antitrypsin mutations (AAT) with the risk of lung cancer in never-smokers, and ascertain if there is an effect modification between these polymorphisms and residential radon exposure.
CONCLUSIONS Taken together, T-77C and Arg399Gln polymorphisms of the XRCC1 gene, as well as the 186C>T and Val158Met polymorphisms of the COMT gene, increased the risk of lung cancer in non-smoking women, with the factors of occupation type, cooking-oil fumes, and soot exposures representing key contributing factors.
The polymorphic variants within the XRCC1 gene have found to play an important role in overall survival of lung cancer patients undergoing specific chemotherapy regimen.
Haplotype analysis illustrated haplotype block 11 (CGAGG) carrying minor allele for XRCC1 206 was associated with the highest risk towards lung cancer on the contrary block 4 (CAGAG) carrying mutant allele for XRCC1 399 significantly decreased the risk.
In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.
These preliminary results suggested that the XRCC1 c.482C>T and c.1686C>G genetic variants might play genetic effects on the susceptibility to lung cancer in the studied population.
In the present study, we investigated the polymorphisms of the following selected members of the base and nucleotide excision repair genes: XPC (Lys939Gln), XPD (Lys751Gln), XRCC1(Arg399Gln), and hOGG1(Ser326Ser), and the risk they present toward the development of lung cancer, with emphasis on the effect of chromium exposure.
XRCC1 is an important scaffold protein involved in base excision repair that is regulated by ERK1/2 and AKT signals and plays an important role in the development of lung cancer.
Additionally, four polymorphisms of XRCC1 (rs25487, rs25489, rs1799782, and rs3213245), which were investigated with regard to their association with lung cancer risk in previous studies, were also genotyped.
Their results suggest that codon 399 polymorphism of XRCC1 gene might contribute to individual's susceptibility to lung cancer in Asian population and especially in nonsmoking Chinese women.The result is encouraging.
When stratified by source of control, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-based controls (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype on the basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43).
Taken together, these findings show that the functional c.1161G>A and c.1779C>G genetic variants of XRCC1 are associated with lung cancer susceptibility in the Chinese Han populations and might be used as molecular markers for evaluating the risk of lung cancer.
We found that three variants in CYP1A1, GSTM1, and XRCC1 showed consistently significant associations with lung cancer in mixed analysis and stratified analysis, and several variants showed diverse effects interacting with different environmental factors in stratified analysis.
These preliminary results suggested that the XRCC1 c.1178G>A genetic polymorphism is statistically associated with lung cancer risk in the Chinese population.
The pooled results showed that there was a significant association between XRCC1rs3213245 polymorphism and lung cancer risk (allele model: OR =1.31, 95% CI 1.13-1.51, P < 0.001; homozygote model: OR = 1.42, 95% CI 1.13-1.79, P = 0.003; recessive model: OR = 1.39, 95% CI 1.13-1.71, P = 0.002; dominant model: OR = 1.31, 95% CI 1.17-1.47, P < 0.001).
The result involving 8,876 lung cancer patients and 11,210 controls revealed that XRCC1Arg194Trp polymorphism was not associated with lung cancer risk [(OR=0.97, 95 %CI=0.92-1.03) for Trp vs. Arg; (OR=0.92, 95 % CI=0.85-0.98) for ArgTrp vs. ArgArg; (OR=1.07, 95 % CI=0.92-1.23) for TrpTrp vs. ArgArg; (OR=0.93, 95 % CI=0.87-1.00) for (TrpTrp + ArgTrp) vs. ArgArg; and (OR=1.08, 95 % CI=0.94-1.25) for TrpTrp vs. (ArgTrp + ArgArg)].