Association Of Gene Polymorphisms In Genes JWA XRCC1 And The Effect Of Chemosensitivity To Anticancer Drugs In Lung Cancer Patients

Background:Along with the air pollution, industrialization, various biochemical factors,and smoking, lung cancer has become a huge threat to human health and life as a fastest growing morbidity and mortality of malignant tumor. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of lung cancer, about 30%-40% of NSCLC have lost surgical excision opportunities because late diagnosis. The current standard of first-line chemotherapy for advanced NSCLC patients of platinum drugs on MDT. How to forecast NSCLC sensitivity to chemotherapy drugs, to guide the chemotherapy drug selection and implementation of individualized treatment is of great importance. JWA gene is associated with cell differentiation regulation of new sample cytoskeleton genes. DNA repair gene XRCC1 is base excision repair/an important ingredient in single fracture repair system, involved DNA damage repair process. In recent years, the JWA, XRCC1 and a lot of progress has been made in research on the correlation of malignant tumor, the two gene polymorphism and efficacy of chemotherapy correlation is also a research hotspot in recent years. By PCR-RFLP technique to detect the patient’s genetic model has the advantages of the method is simple, fast, don’t need to collect carcinoma tissue samples, can overcome not surgery, especially in patients with late cannot obtain specimens is difficult, the research method is feasible.Objective:By immunohistochemistry and PCR-RFLP technique respectively into the group of patients with lung cance blood samples were JAW and XRCC1 gene type detection. Analysis of genetic polymorphisms of the classification and correlation, the efficacy of chemotherapy through clear JAW and XRCC1 gene polymorphisms in the prediction value of lung cancer chemotherapy curative effect, and ultimately benefit from more patients with lung cancer.Methods:JWA and XRCC1 gene type was tested into the group of patients with lung cancer blood specimen. Analysis of JWA and XRCC1 gene polymorphisms of the classification and correlation, the efficacy of chemotherapy with SPSS 19.0 statistical software for statistical data processing.Results:The experimental results show that the lung cacer patients with JWA gene JWA 723T>G of TT, TG, GG genotypes, chemotherapy disease control rates (CR+PR+SD) are 73.17%, 67.35% and 42.86% respectively, with JWA gene JWA 454 A>C of AA, CA, patients with CC genotype, chemotherapy disease control rates (CR+PR+SD) was 73.33%,66.67% and 50.00% respectively. JWA723 T>G genotype of disease control rates comparison, difference was not statistically significant (chi-square=4.34, P=0.11). The JWA 454 A>C genotype of disease control rates comparison, difference was not statistically significant (chi-square=4.42, P=0.11). XRCC1 gene Codon194 Trp/Trp、Arg/Trp、Arg/Arg genotypes of patients, chemotherapy disease control rates (CR+PR+SD) are 78.57%,65.85% and 42.86% respectively, carrying XRCCl gene Codon399 Arg/Arg、Arg/Gln and Gln/Gln genotype patients, chemotherapy disease control rates (CR+PR+SD) was 79.63%, 56.10% and 33.33% respectively. Codon194 genotype of disease control rates comparison, difference was statistically significant (chi-square=8.01, P=0.02). Codon399 genotypes of disease control rates comparison, difference was statistically significant (chi-square=10.58, P=0.01). Carry Codon194 Arg/Arg genotype in patients with chemotherapy failure risk is to carry Trp/Trp genotype individual 1.83 times (78.57%VS42.86%; OR=1.83,95%CI:1.09-3.08; P<0.05). Carrying Codon194 Arg/Trp genotype in patients with chemotherapy failure risk is to carry Trp/Trp genotype individual 1.54 times (65.85%VS 42.86%; OR=1.54,95% CI:0.89-2.64, P=0.02). Carrying Codon399 Gln/Gln genotypes in patients with chemotherapy failure risk is to carry Codon399Arg/Arg genotype individual 2.39 times (79.63% VS 33.33%; OR=1.68,95%CI:0.94-6.08; P=0.03). Carrying Codon399 Arg/Gln genotypes in patients with chemotherapy failure risk is to carry Arg/Arg genotype individuall.68times(56.10%VS33.33%;OR=1.68,95%CI:0.64-4.41;P=0.02).Carrying Codon 194Arg/Arg and Codon399Gln/Gln genotypes in patients with chemotherapy failure risk are to carry Codon194 Trp/Trp+Codon399Arg/Arg genotype individual 3.2 times (80.00%VS 25.00%; OR=3.2,95%CI:0.58-17.67;P=0.02); Carrying Codon 194 Arg/Trp and Codon399Arg/Gln genotypes in patients with chemotherapy failure risk is to carry Codon194 Trp/Trp and Codon399Arg/Arg genotype individual 3.0 times (75.00% VS 25.00%; OR=3.0,95% CI:0.31～16.69; P=0.03). XRCC1Codon194 Trp/Trp and Codon399Arg/Arg genotype of PFS are the same group was statistically significant, prompted the two genotypes are more sensitive to platinum drugs. JWA gene type and type of XRCC1 gene are no obvious correlation with the incidence of adverse reaction of chemotherapy.Conclusion:1.XRCC1 gene polymorphisms with Codon194 Trp/Trp and Codon399Arg/Arg alleles in patients with lung cancer is sensitive to the platinum drugs, prompt XRCC1 genotypes in patients before chemotherapy, can to some extent on the sensitivity of the platinum drugs in patients with lung cancer.2. JWA gene polymorphisms of prediction on the basis of the platinum chemotherapy regimens the curative effect of treatment of advanced lung cancer has no clinical significance.