This meta-analysis has demonstrated 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.
Gln/Gln alleles of both XRCC1 and XPD genes appear to amplify the effects of household exposure, smoking and betel quid chewing on lung cancer risk in the study population.
In conclusion, this meta-analysis indicates that XRCC1 -77T>C shows an increased lung cancer risk and XRCC3 T241M polymorphism is associated with decreased lung cancer risk, especially in Caucasians.
To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met) genes with lung cancer risk in northeastern Chinese.
Meta-analysis of 18 studies with high quality also found that there was an obvious association between XRCC1Arg399Gln polymorphism and increased risk of lung cancer under three genetic models.
Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively.
Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility.
In conclusion, this meta-analysis has demonstrated that codon 194, codon 399 and -77 T > C polymorphisms of XRCC1 gene might have contributed to individual susceptibility to lung cancer.
This meta-analysis aimed to summarize published data on the association between the commonest SNPs of XRCC1 (rs1799782" genes_norm="7515">Arg194Trp, C > T, rs1799782 and Arg399Gln, G > A, rs25487) and clinical outcome of lung cancer patients.
SNPs associated with lung cancer prognosis primarily mapped to 14 genes in different repair pathways, and 6 SNPs were remained in the final model after multivariate stepwise Cox regression analysis: ATM rs189037; MRE11A rs11020802; ERCC2 rs1799793; MBD4 rs140693; XRCC1rs25487, and PMS1 rs5742933.
In a hospital-based, case-control study of 455 lung cancer cases and 443 cancer-free hospital controls, the SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their correlation with the risk of lung cancer in multivariate logistic regression models.
Compared with carriers of either XRCC1 194Trp homozygote or RAD9 239Arg heterozygote variants, noncarriers were at a significantly decreased risk for lung cancer (odds ratio [OR], 0.282; confidence interval [CI], 0.089-0.893).
Previous studies have suggested that certain genetic polymorphisms, specifically the Xeroderma pigmentosum group D (XPD) gene codon 751 and the X-ray repair cross-complementing group 1 (XRCC1) gene codon 399 polymorphisms, were associated with an increased risk of lung cancer, and, in some studies, with a greater risk for mutations in the p53 tumor suppressor gene in lung tumors.
Our meta-analysis on 2861 cases (lung cancer patients) and 2783 controls from eight eligible studies in Chinese populations showed that for the XRCC1Arg194Trp polymorphism, compared with the Arg/Arg homozygous genotype, the variant Arg/Trp and Trp/Trp genotypes combined was not associated with lung cancer risk (OR=1.06, 95% confidence interval [CI]=0.89-1.27) (Z=0.70, P=0.48), nor was Arg280His (OR=0.63, 95% CI=0.28-1.41) (Z=1.12, P=0.26); however, for the XRCC1Arg399Gln polymorphism, the combination of variant Arg/Gln and Gln/Gln genotypes was borderline significantly associated with lung cancer risk (OR=1.16, 95% CI=1.00-1.36) (Z=1.90, P=0.06), compared with the Arg/Arg homozygous genotype.
In an effort to develop a biomarker for lung cancer risk, we evaluated the transcript expressions of 14 antioxidant, DNA repair, and transcription factor genes in normal bronchial epithelial cells (HUGO names CAT, CEBPG, E2F1, ERCC4, ERCC5, GPX1, GPX3, GSTM3, GSTP1, GSTT1, GSTZ1, MGST1, SOD1, and XRCC1).
These findings further suggest that the polymorphisms XRCC1Arg194Trp and Pro206Pro or the haplotype encompassing the variant alleles may contribute to susceptibility of lung cancer in a Chinese population.
Requiring more stringent P values to account for multiplicity of comparisons, only the associations of ERCC2 codon 751 (recessive model) and of XRCC1 -77 T>C (dominant model) with lung cancer had P <or= .0001 and retained P <or= .001 even when the first published studies on the respective associations were excluded.
Lung cancer risk associated with individual SNPs was seen for GSTP1 [A allele; odds ratio (OR) = 1.85; 95% confidence interval (CI), 1.04-3.27] and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01-2.79) in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18-104) in black women smokers.