| Objective:The aim of this study is to investigate the relationship between single base polymorisms of XRCC1 G28152 A, MUTYH G972 C, HOGG1 C1245 G, PARP1 T2444 C, MTHFR C677 T and the sensitivity of chemotherapy and clinical outcome in patients with advanced non-small cell lung cancer treated with platinum based chemotherapy. Methods:During the period from November 2009 to January 2016, a total of 152 patients diagnosed with IIIB or IV stage non-small cell lung cancer by pathological diagnosis in our hospital were admitted into our study. The XRCC1 G28152 A, MUTYH G972 C, HOGG1 C1245 G, PARP1 T2444 C and MTHFR C677 T polymorphisms of all the patients were detected by the mass spectrometry. The results used statistical analysis by χ2 test, Logistic regression, Kaplan-Meier survival curve and Cox regression. Results:χ2 test showed that patients with smoking history or not had different efficiency rates of chemotherapy(p=0.002). There was statistical significant difference in the efficiency rates of chemotherapy of different pathological types(P=0.028). Logistic regression model suggests that effective rate of chemotherapy for smoking patients was higher than non-smoking patients(OR=3.411,95%CI: 1.469-7.920,P=0.004). The effective rate of chemotherapy in patients with adenocarcinoma was higher than that in patients with squamous cell carcinoma, but there was no statistical significance(OR=1.887,95%CI: 0.753-4.732,P=0.176), the effective rate of chemotherapy in patients with large cell carcinoma was significantly higher than that in patients with squamous cell carcinoma, and the difference was statistically significant(OR=7.579, 95%CI:1.041-55.173,P=0.046). The efficiency rate of chemotherapy of patients with PARP1 2444 TT, CC and TC genotype was 9/44(20.5%), 15/28(53.6%) and 28/76(36.8%). Logistic regression model showed that the effective rate of chemotherapy of the CC genotype was significantly higher than the TT wild type(OR: 5.216, 95%CI: 1.568-17.352, P= 0.007). The effective rate of chemotherapy of TC genotype was higher than that of TT wild type(OR: 2.692, 95%CI: 1.007-7.198, P=0.048). The effective rate of chemotherapy in patients with at least one mutant genes(TC+CC) was higher than that with wild type(OR:3.178, 95%CI:1.229-8.219, P = 0.017). There was no significant correlation between G28152 A, MUTYH G972 C, XRCC1 HOGG1 C1245 G, MTHFR C677 T gene polymorphism and chemosensitivity. Kaplan-Meier survival curve showed that there were no statistically significant differents in the PFS and OS of different genotypes of MUTYH G28152 A, XRCC1 G972 C, HOGG1 C1245 G, PARP1 T2444 C and MTHFR C677T(P>0.05). Cox regression multivariate analysis revealed that the risk of death was significantly higher in patients with XRCC1 28152 GA than in wild type(HR: 1.667, 95%CI: 1.048-2.650, P= 0.031). There was no significant correlationship between the other genotypes and the prognosis. Conclusions:1.χ2 test shows that there is a statistically significant effect of smoking history and pathological types of patients with chemotherapy efficiency. Single factor analysis of Logistic regression model shows that the effective rate of chemotherapy in patients with advanced non-small cell lung cancer with smoking history are significantly higher than those with advanced non small cell lung cancer patients who have no history of smoking. The effective rate of chemotherapy in patients with adenocarcinoma is higher than that in the patients with squamous cell carcinoma, but the difference is not statistically significant.2.PARP1 2444 mutation allele C may be associated with decreased sensitivity to platinum based chemotherapy in advanced non small cell lung cancer.3.XRCC1 28152 GA heterozygous type may be associated with poor prognosis of advanced NSCLC treated with platinum.4.The polymorphisms of XRCC1 G28152 A, MUTYH G972 C and HOGG1 C1245 G gene is not related to the prognosis of advanced NSCLC.5.The polymorphisms of MUTYH G972 C, HOGG1 C1245 G and PARP1 T2444 C gene are not related to the prognosis of advanced NSCLC.6.The polymorphism of MTHFR C677 T gene have no relationship between the effective rate of platinum combined chemotherapy and the prognosis of patients with advanced NSCLC. |
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