The Association Of XRCC1 Polymorphism With The Risk Of Gastric Cardiac Adenocarcinoma

Objective: Both environmental carcinogen and product of metabolism may induce DNA damage, therefore, the biology mainly depend on a series of DNA repair pathways to maintain the genomic stability and integrity. The protein encoded by the human XRCC1 gene was considered to play an important role in the base excision repair and single-strand break repair processes. The genetic polymorphisms of XRCC1 might be able to influence DNA repair ability, which might be associated with risk of developing cancer. This study was designed to investigate the correlation of XRCC1 Arg194Trp Arg399Gln Arg280His SNPs with the risk of GCA.Methods: This population-based case-control study included 455 GCA patients and 650 healthy controls. Genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. Polymorphisms of XRCC1 gene were analyzed by PCR-restriction fragment length polymorphism analysis (RFLP).Statistical analysis was performed using SPSS11.5 software package. P<0.05 was considered significant for all statistical analyses. Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. Comparison of the XRCC1 genotype, allelotype and haplotype distribution in cancer patients and healthy controls was performed by means of two-sided contingency tables using Chi-square test. The odds ratio (OR) and 95% confidence Interval (CI) were calculated using an unconditional logistic regression mode. The haplotype frequencies were estimated by using EH linkage software.Results1. The genotype frequencies of XRCC1 Arg194Trp Arg280His and Arg399Gln in healthy controls did not significantly deviate from that expected for a Hardy-Weinberg equilibrium (P>0.05).2. The frequencies of the XRCC1 Arg194Trp Arg and Trp allele among GCA patients and healthy controls were 67.6% 32.4% and 68.8% 31.2% respectively; No significant difference in the XRCC1 allele distribution was shown between GCA patients and controls (P>0.05). The distribution of the Arg/Arg, Arg/Trp and Trp/Trp genotypes between GCA patients (47.5%, 40.2% and 12.3%, respectively) and controls (48.8%, 40.2% and 11.0%, respectively) also had no significant difference (P>0.05). Compared with the Arg/Arg genotypes, the Arg/Trp and Trp/Trp genotypes could not increase the risk of developing GCA, the odds ratio was 1.02 (95%CI=0.79~1.32) and 1.13 (95%CI=0.76~1.68). When stratified for the family history of UGIC and smoking status, no significant difference in genotype and allele distributions was found between patients and control groups in XRCC1 Arg194Trp ( P >0.05).3. The frequencies of the XRCC1 Arg280His Arg and His allele among GCA patients and healthy controls were 89.3%, 10.7% and 90.5%, 9.5% respectively; No significant difference in the XRCC1 allele distribution was shown between GCA patients and controls (P>0.05). The distribution of the Arg/Arg, Arg/ His and His/His genotypes between GCA patients (79.6%, 19.6% and 0.9%, respectively) and controls (82.0%, 16.9%和1.1%, respectively) also had no significant difference (P>0.05). Compared with the Arg/Arg genotypes, the Arg/His and His/His genotype could not significantly increase the risk of GCA, with an OR 1.14 (95%CI=0.84-1.55). When stratified for the smoking status, The Arg280His + His280His genotypes significantly increased the risk for developing GCA among smoking patients compared with the Arg280Arg with an OR of 1.57 (95%CI=1.00-2.51). When stratified for the family history of UGIC, no significant association between the Arg280His SNP and the risk of developing GCA was found.4. The frequencies of the XRCC1 Arg399Gln Arg and Gln allele among GCA patients and healthy controls were 74.0%, 26.0% and 73.8%, 26.2%, respectively; No significant difference in the XRCC1 allele distribution was shown between GCA patients and controls (P>0.05). The distribution of the Arg/Arg, Arg/Gln and Gln/Gln genotypes between GCA patients (53.0%, 42.0% and 5.0%, respectively) and controls (53.1%, 41.5%和5.4%, respectively) also had no significant difference (P>0.05). Compared with the Arg/Arg genotypes, the Arg/Gln and Gln/Gln genotypes could not increase the risk of developing GCA, the OR were 0.80 (95%CI=0.60~1.05) and 1.31 (95%CI=0.74~2.33). When stratified for the family history of UGIC and smoking status, no significant difference in genotype and allele distributions was found between patients and control groups in XRCC1 Arg399Gln ( P>0.05).5. The haplotypes were analyzed by 2LD software. The CGG TGG CGA CAG were the common haplotypes. No significant differences were found between the two groups in the distribution of haplotype(P>0.05), compared with the haplotype of CGG, other haplotypes didn't increase the risk of developing GCA .Conclusions1. The XRCC1 Arg194Trp and Arg399Gln SNPs might not be related to the risk of GCA development.2. There was no significant association between the XRCC1 Arg280His SNP and the risk of developing GCA in overall people. However, smokers with His allele at codon 280 had a significantly increased the risk of GCA.3. The haplotype distribution of XRCC1 Arg194Trp Arg280His and Arg399Gln SNPs had no influence on the risk of GCA.