These findings indicate that these tagSNPs of the ERCC2 and ERCC3 along with their surrounding regions may serve as biomarkers of susceptibility to lung cancer, which warrant further validation by other population-based and phenotypic studies to determine the biological relevance of these tagSNPs.
As a result, 15 SNPs on or near 12 genes and one miRNA with strong evidence of association with lung cancer risk were identified, including TERT (rs2736098), CHRNA3 (rs1051730), AGPHD1 (rs8034191), CLPTM1L (rs401681 and rs402710), BAT3 (rs3117582), TRNAA (rs4324798), ERCC2 (Lys751Gln), miR-146a2 (rs2910164), CYP1B1 (Arg48Gly), GSTM1 (null/present), SOD2 (C47T), IL-10 (-592C/A and -819C/T), and TP53 (intron 6).
Two of the genetic polymorphisms, XRCC1Arg399Gln and XPDLys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive.
Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR = 0.40, 95% CI 0.19-0.85) compared to the most common haplotype.
A pertinent combination of multiple "at-risk" genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2rs13181 was at a 5.94-fold (95% CI = 2.77-12.7) increased risk of lung cancer.
This meta-analysis suggests that the XPDLys751Gln and Asp312Asn gene polymorphisms are associated with lung cancer risk, the C allele of XPDLys751Gln genotype is an increased risk factor for developing lung cancer among Caucasians and in smokers, and the A allele of XPD 312 genotype is also an increased risk factor among Asians and in smokers.
We discovered that polymorphisms in the XPD gene in men [log-additive model: odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.17-2.31], the ATM gene in women and nonsmokers (codominant model: OR = 0.11, 95% CI: 0.02-0.49 and OR = 0.25, 95% CI: 0.08-0.72, respectively), the APEX1 gene for smokers (recessive model: OR = 2.55, 95% CI: 1.34-4.85), and the NBS1 gene for those who work in the coal industry (overdominant model: OR = 0.40, 95% CI: 0.21-0.75) are associated with an increased risk of lung cancer.
From MDR analysis, in Latinos, smoking and 3 SNPs (ERCC2rs171140, ERCC5 rs17655 and LIG1 rs20581) together had a prediction accuracy of 67.4% (p = 0.001) for lung cancer.
Among men, carriers of the variant allele of XPDLys751Gln had a non-significantly increased risk of lung cancer in the youngest age interval (RR=6.38, 95% CI=0.74-54.90).
Combinations of polymorphisms in genes involved in the same repair pathway (XPA + XPD or XRCC1 + APE1) affected lung cancer risk only in patients with SCC.
The XPD codon 312 Asp/Asp genotype was found to have almost twice the risk of lung cancer when the Asp/Asn + Asn/Asn combined genotype served as reference [odds ratio (OR) 1.86, 95% confidence interval (CI), 1.02-3.40].
In this case-control study of 1091 Caucasian lung cancer patients and 1240 controls, we explored the gene-environment interactions between the XRCC1 Arg399Gln polymorphism, alone or in combination with the two ERCC2 polymorphisms, and cumulative smoking exposure in the development of lung cancer.
Using a panel of 20 lung cancer cell lines, including 15 NSCLC and 5 small cell lung cancers (SCLC), the mRNA expression levels for the RRM1, ERCC1 and ERCC2 genes were examined by quantitative real-time reverse transcription PCR.
We therefore examined XPD polymorphisms at Lys751Gln and Asp312Asn in 341 white lung cancer cases and 360 age-, sex-, ethnicity-, and smoking-matched controls accrued in a hospital-based molecular epidemiological study of susceptibility markers for lung cancer.
Furthermore, single nucleotide polymorphisms (SNPs) and haplotypes in the ERCC2 gene are thought to be associated with the risk of developing lung cancer and clinical outcomes.
We found an increased risk of lung cancer among subjects carrying the ERCC2 751Gln/Gln genotype (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.14 - 1.49).
In conclusion, this study indicated no association between mRNA expression of the DNA-repair genes ERCC1 and XPD and risk of subsequent development of lung cancer.
In conclusion, this meta-analysis suggests that the two ERCC2 polymorphisms may contribute to lung cancer susceptibility serving as low-penetrance risk factors.
We therefore tested the hypothesis that these two XPD polymorphisms are associated with susceptibility to lung cancer in a hospital-based, case-control study in a Chinese population.
Although none of the six htSNPs was individually associated with lung cancer risk, we found that two ERCC2 haplotypes were associated with risk of lung cancer.
In conclusion, the APE1 Asp148Glu polymorphism is highly predictive for lung cancer, and cumulative cigarette smoking modifies the associations between the XRCC1 Arg399Gln and the XPDLys751Gln polymorphisms and lung cancer risk.