The Investigation Of Correlation Between XPG And XRCC1 Gene Polymorphism And Effect Of Oxaliplatin For Advanced Gastric Cancer

BackgroundGastric cancer is one of the most common malignant tumor of the digestive canal in China, yet most diagnoses are belong to the advanced stage. So the chemotherapy is one of the effective and important method for advanced gastric cancer diagnoses. The oxaliplatin is mainly used for the gastric cancer, but the therapeutic effect has the individual difference. It is not realted with the bliological behavior of the gastric cancer cells but also the individual sensibility to the drugs. Research shows that nucleotide excision repair (NER) and base excision repair (BER) may be an important mechanism of oxaliplatin resistant. And the xerodernm pigmentosum group G (XPG) and x-ray repair cross-complementing gene 1(XRCC1) are the key genes in NER and BER pathways reppectively.The purpose of this test is to investigate the relationship between the two gene polymorphisms and the sensibility of the oxaliplatin on the advanced gastric cancer.ObjectiveBy means of XPG and XRCC1 expression were detected in different, the influence of single nucleotide polymorphism of chemotherapeutic drugs for gastric cancer key metabolic gene on the acceptability of the efficacy of Oxalipiatin regimen for patients with advanced gastric cancer. To provide guidance for clinical progress of gastric cancer and the choice of chemotherapy, conducive to the implementation of individualized treatment.MethodsRespectively by PCR-RFLP method from January 2013 to December 2013, works group of patients with advanced gastric cancer blood specimen test XPG and XRCC1 gene type. Analysis of the correlation of XPG and XRCC1 gene polymorphisms and the efficacy of chemotherapy with SPSS 19.0 statistical software for statistical data processing..Results(1) For the XPG genotype frequency distribution of C46T:type C/C 62.50%, type C/T 25.00%, type T/T 12.50%. C/C wild genotype patients the disease control rates was 86.67%(26/30), C/T+T/T genotype 55.56%(10/18), comparing the two groups, the difference was statistically significant (χ2=5.807, P=0.016). Into the group of patients with Logistic regression statistical correction factors such as age, gender, XPG genotype associated with chemotherapy sensitivity is obviously (P= 0.040), the number of OR is 1.560(95%CI=1.008-10.413), suggesting that the site prediction-SNP can be used as a short-term effect of oxaliplatin in the treatment of patients with gastric cancer marker. In 48 cases of gastric cancer patients in a time of disease progression (PFS) is 6.5 months and median PFS C/C genotype for 7.4 months, T/T and C/T genotype of median PFS was 4.6 months, with statistical significance (P= 0.003).Cox proportional hazards models to analyze influencing factors:such as age, gender, etc., after correction XPG genotype and PFS is still are closely associated with (OR=2.491,95% CI=1.324-9.725), suggesting that the site prediction index SNP can be used as a long term effect of oxaliplatin in the treatment of patients with gastric cancer.XPGC46T gene polymorphism can be used as a screening indexes of chemotherapy in advanced gastric cancer before selection, individualized treatment for patients with chemotherapy drug sensitive genotypes.(2) The XRCC1 gene Arg399GLn dispersed frequency for dyeing size:G/G type 52.08%, and type G/A 41.67%, type A/A 6.25%. G/G wild genotype patients the disease control rates was 88%(22/25), G/A+A/A genotype 60.87%(14/23), comparing the two groups, the difference was statistically significant (χ2=4.703, P=0.030). Into the group of patients with Logistic regression statistical correction factors such as age, gender, XRCC1 gene polymorphisms associated with chemotherapy sensitivity is obviously (P=0.036), the number of OR is 1.575, suggesting that the site prediction-SNP can be used as a short-term effect of oxaliplatin in the treatment of patients with gastric cancer marker. In 48 cases of gastric cancer patients in A time of disease progression (PFS) is 6.5 months and the median PFS to G/G genotype for 7.5 months, G/A and A/A genotype of median PFS was 5.5 months, comparison was statistically significant (P=0.007). Cox proportional hazards models to analyze influencing factors:such as age, gender, etc., after the correction of XRCC1 gene type and PFS is still are closely associated with (OR=3.412,95% CI=1.057-4.698), suggesting that the site prediction index SNP can be used as a long term effect of oxaliplatin in the treatment of patients with gastric cancer. XRCC1 gene polymorphism can be used as a screening indexes of chemotherapy in advanced gastric cancer before selection, individualized treatment for patients with chemotherapy drug sensitive genotypes.(3) Cox proportional hazards models to analyze the median PFS, XPG C/C and XRCC1 G/G genotype was 8.6 months, XPG C/C and XRCC1 G/A+A/A genotype was 6.5 months, XPG C/T+T/T and XRCC1 G/G genotype was 5.9 months, XPG C/T+T/T and XRCC1 G/A+A/A genotype was 3.4 months, comparison was statistically significant (P<0.001).Conclusion1. XPG gene type C/C, XRCC1 gene type G/G in patients with advanced gastric cancer is sensitive to give priority to the oxaliplatin-based chemotherapy, prompt before chemotherapy for patients with XPG and XRCC1 gene detection, to a certain extent can be predicted for advanced gastric cancer patients is given priority to with oxaliplatin into the sensitivity of chemotherapy regimens.2. There showed a correlation between XPG and XRCC1 gene polymorphisms and the median PFS of oxaliplatin based chemotherapy in the treatment of advanced gastric cancer patients, the detection results can be used as a reference for selecting oxaliplatin chemotherapy for gastric cancer.