Polymorphism In The5’-untranslated Region Of Thymidylate Synthase Gene And Sensitivity Of Advanced Non-small Cell Lung Cancer To Pemetrexed

Objective:Through the detection of the single nucleotide polymorphisms in the5’-untranslated region of thymidylate synthase (untranslated region, UTR) genotype in the patients with advanced non-small cell lung cancer, to investigate the relationship between polymorphism in the5’-untranslated region of thymidylate synthase gene and sensitivity of advanced non-small cell lung cancer to pemetrexed. To provide data of predictors of individual therapy for patients with advanced non-small cell lung cancer.Method:We retrospectively analyzed twenty-nine advanced Nsclc patients in the Second Xiangya hospital of Central South University and Hunan Province Tumor Hospital from January2012to May2013. All the patients were taken the pemetrxed regimen (500mg/m2on Day1) for every21days.Evaluated the efficacy after two consecutive cycles.Evaluated the toxicity after one cycles. Twenty-nine patients were analyzed by the indicators such as ORR (objective response rate),PFS (progress free survival), adverse effects rate and so on. The TS gene polymorphism in patients’peripheral blood was tested by short tandem repeat-polymerase chain reaction and capillary electrophoresis. Data were analyzed statistically by using SPSS18.0statistical software.Results:(1) The gene frequency of the TS gene polymorphism in29patients with nonsmall-cell lung cancer were2G8.6%,2C6.9%,3G34.5%,3C50.0%;(2) Among the29patients, no one was in complete remission,18patients had partial response,10stable disease and1progressive disease. The objective response rate was62.1%. Low expression group was accounted for76.9%(10/13) and High expression group was for50%(8/16), there was no statistical significant difference between two groups.(P>0.05)(3) The main side effects was gastrointestinal which occurred with grade1～2in13.8%(10/18).The most dangerous side effects was neutropenia which occurred with grade1～2in51.7%(15/29).There were no obvious heart and hepatorenal harm,nor treatment-related death. TS gene types in the patients have no statistically significant (P>0.05)(4) Low expression group and High expression group of patients have statistically significant difference in the median PFS (7.0months vs3.0months,χ2=4.301, P=0.038).Low expression group has significant advantage in PFS. Conclusion:(1) The low expression group(3G/3G,2R/3G,3G/3C) acounting for44.8%, the high expression group (2R/2R,2R/3C,3C/3C) acounting for55.2%。(2) The low expression group effective rate was76.9%, the high expression group effective rate was50.0%. The low expression group has a higher efficiency than the high group, but this result has no statistical significance; TS genetype has no relationship with toxicity reaction.(3) Low expression group has significant advantage in PFS.There existed a significant difference between the higher expression groups and lower ones in the expression of surviving. Picture4;table7;reference77.