Polymorphism In The3’-untranslated Region Of Thymidylate Synthase Gene And Sensitivity Of Advanced Lung Adenocarcinoma To Pemetrexed

ObjectiveThrough inspection in patients with advanced lung adenocarcinomaPolymorphism in the3′-untranslated region of thymidylate synthase gene（untranslated region, UTR）1494bp place6bp missing or insert polymorphism（-6bp or+6bp） genotype, investigate the relationship between Polymorphismin the3′-untranslated region of thymidylate synthase gene and sensitivity ofadvanced lung adenocarcinoma to pemetrexed. To provide the data forpatients with advanced lung adenocarcinoma predictors of individual therapy.MethodsThe Aollg^TM probe combined with real-time fluorescence PCR technologytesting accept pemetrexed scheme of106cases of chemotherapy in patientsFrom January2008to March2010in liaoning medical school affiliated hospitaloncology first hospital treatment, by pathological or cytology diagnosed and aline treatment failure or recurrent advanced （Ⅲ b-Ⅳ period） with lungadenocarcinoma in peripheral blood genotype TS, analysis carry TS differentgenotypes of the relationship between patients and chemotherapy sensitivity.Using the phone or outpatient service follow-up follow-up data collection way,analyzes carry different genotypes of TS patients and chemotherapy sensitivityof the relationship.Results（1）106cases in patients with advanced lung adenocarcinoma TS gene3’-UTR1494bp place6bp missing or insert polymorphism gene frequencyrespectively:-6bp/-6bp55.7%（59/106），-6bp/+6bp44.3%（47/106）， +6bp/+6bp0%（0/106）（2） Gender, pathological types, TS gene types in the patients withsignificant （P <0.05）, age ECOG score and recent efficient business.-6bp/-6bp;-6bp/+6bp cases were59patients,47cases). Effective rate was32.20%（19/59）,12.77%（6/47）, two groups of comparisons difference wasstatistically significant （the chi-square=5.432, P <0.020）.（3） The overall response rate was23.58%, Carry TS gene3′-UTR1494bp place-6bp/-6bp genotype chemotherapy efficient carry-6bp/+6bpgenotype efficient4.382times（95%CI,1.462～13.130,P=0.008）；（4） Carry-6bp/-6bp genotype and carry-6bp/+6bp genotypes ofpatients in the median PFS, median OS difference have statistically significant（3.400months vs2.477months，P=0.001；14.239months vs12.194months，P=0.000）；tip carry-6bp/-6bp genotypes in patients with significant advantageOS, PFS.（5） Cox regression analysis the clinical pathologic factors and therelationship between the survival time that the bigger the age, the laterpathology stage,carry TS3’-UTR1494bp place-6bp/+6bp genotype death riskmore big.Conclusions（1） TS gene3′-UTR1494bp place-6bp/-6bp genotype chemotherapythan efficient carry six bp/+6bp gene type high efficient, carry-6bp/-6bpgenotype patients in PFS, OS has significant advantage. Age is smaller,pathological staging the earlier, TS3’UTR1494sites place-6bp/-6bp geneprognosis of patients with type is better.（2） TS gene3’UTR1494bp place6bp missing or insert polymorphism （6bp or+6bp） may be late with lung adenocarcinoma patients beauty whichsong plug scheme chemotherapy sensitivity related, the late may act as a lungadenocarcinoma patients predictors of individual therapy.