| ObjectiveTo explore the relationship of two single-nucleotide polymorphisms in XPD(xeroderma pigmentosum group D) gene loci, Gene-environment interaction and esophageal cancer, to provide a theoretical basis for revealling the etiology of esophageal cancer and developing intervention measures of esophageal cancer(EC).MethodsA comprehensive search was conducted to identify all case-control studies of XPD codon 312 and codon 751 polymorphisms and EC risk. The Meta-analysis was applied with RevMan4.2 software for calculation of pooled OR value (with 95% CI) of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarci-noma (EAC).In Han population from Henan province a case-control study was conducted to explore the relationship between XPD gene polymorphisms and ESCC risk.Results1. Meta analysis resultsCodon 312:Compared with the wild-type homozygote GG, the pooled Odds Ratio (with 95% CI) of XPD codon 312 genotype for EC risk GA, AA and (GA+AA) was 1.12(0.94,1.33),1.32 (0.94,1.84),1.14(0.96,1.34), respectively.Codon 751:Compared with the wild-type homozygote AA, the pooled Odds Ratio (with 95% CI) of XPD codon 751 genotype AC, CC, (AC+CC) for EC risk was 1.19(1.05,1.34),1.22(0.86,1.74),1.20(1.01,1.42), respectively. In a stratified analysis, individuals carrying AA genotype or (AA+AC) had 1.22-fold or 1.24-fold excess risks for ESCC compared with those carrying AA genotype, and any genotype of XPD codon 751 genetic polymorphism was not found to be related to EAC.2. Results of case-control study2.1 XPD gene polymorphism and the risk of esophageal squamous cell carcinoma Codon 312:Compared to wild genotype GG, the genotypes of GA, AA and (GA+AA) were not associated with the risk of ESCC, the adjusted OR (95% CI) for ESCC risk was 1.31(0.73,2.36),1.00(0.06,16.56) and 1.30(0.73,2.32), respectively.Codon 751:Compared to wild genotype AA, the genotype of AC, CC and (AC+ CC) were not associated with the risk of ESCC, the adjusted OR (95% CI) for ESCC risk was 1.14(0.77,1.67),0.97(0.44,2.14) and 1.11(0.77,1.61) respectively.2.2 Haplotype analysisThe haplotype GA merged by wild-type alleles served as control haplotype, and the haplotypes GC, AA, and AC were not associated with the risk of ESCC, the OR (95% CI) was 0.99(0.72,1.37),0.91(0.37,2.27) and 1.51(0.76,3.03), respectively.2.3 Combined genotypes analysisCompared with GG/AA genotype combined by wild genotype was served as controls, the other eight kinds of combined genotypes GG/AC, GG/CC, GA/AA, GA/AC, GA/CC, AA/AA, AA/AC, and AA/CC were not associated with the risk of ESCC, the OR (95% CI) was 1.11(0.73,1.68),0.73(0.30,1.76),1.18(0.44,3.15),1.29 (0.60,2.79),3.14(0.32,30.40),1.01(0.99,1.02) and 0.99(0.98,1.01) respectively.2.4 Trend analysis of the number of mutationsThe genotypes with neither mutations in the two sites were served as the control genotype, and the genotypes with a mutation in only one site and two mutation sites in both were not associated with the risk of ESCC, the OR (95% CI) was 1.05(0.71, 1.54),1.50(0.73,3.09) respectively.The genotypes with neither mutation in the four alleles were served as the control genotype, and the genotypes with one allele mutation, two alleles mutation, three or four, were all not associated with the risk of ESCC (P>0.05).2.5 Gene-environment interaction:Compared with non-smoker carrying codon 312 or codon 751 wild genotype, it was failed to discover the interaction of smoking and XPD codon 312 or codon 751 variant genotypes in ESCC developing. Compared with non-drinking carrying codon 312 or codon 751 wild genotype, it was failed to discover the interaction of drinking and XPD codon 312 or codon 751 variant genotypes in ESCC developing. Conclusions1. It was showed in Meta analysis that XPD gene 312 polymorphism may be unrelated to the incidence of EC. Heterozygous genotypes AC and (AC+CC) in XPD 751 polymorphism were risk factors for EC, further, heterozygous genotype AC, and (AC+CC) in XPD 751 polymorphism related with the incidence of ESCC; there was no relationship between XPD 751 polymorphism and the risk of EAC.2. It was showed in case-control studies that XPD gene 312 polymorphism may be unrelated to the incidence of ESCC in Han population from Henan province. XPD gene 751 polymorphism may be unrelated to the incidence of ESCC in Han population from Henan province. Cooperative role between XPD codon 312 and codon 751 had not been found related in the incidence of ESCC in Han population from Henan province. Interactions between smoking or drinking and XPD codon 312 or codon 751 had not been found related in the incidence of ESCC in Han population from Henan province.
|
PDF Full Text Request