Association Between Polymorphisms In Genes Involved In Apoptosis And Drug Metabolism And The Clinical Outcome In Advanced Non-Small-Cell Lung Cancer Patients Treated With Gefitinib

Partâ… :Association between Polymorphisms in FAS,FASL,CASP8 and the Clinical Outcome in Advanced Non-Small-Cell Lung Cancer Patients Treated with GefitinibEpidermal growth factor receptor tyrosine kinase inhibitors play a very important role in the treatment of advanced non-small-cell lung cancer patients.Till now,some clinical and biological predictors have been identified,such as pathological types,sex, smoke,EGFR mutation and EGFR gene copy number,but they all have some limitations.In our study,88 patients with stageâ…¢A,â…¢B andâ…£NSCLC were treated with gefitinib.We investigated the association between polymorphisms in FAS, FASL and CASP8 and the clinical benefit and outcome of these patients.We observed that patients with adenocarcinoma had a significantly higher clinical benefit rate and longer overall survival(P=0.009 and P=0.048,respectively).Longer time from completion of previous chemotherapy were associated with significantly higher clinical benefit rate and longer progression free survival of gefitinib(P=0.003 and P=0.001,respectively).We first documented that FAS-1377 AA genotype carriers had a significantly lower clinical benefit rate compared with GG genotype carriers (P=0.008,OR:0.15,95%CI:0.038-0.614).FAS-670 AG+AA genotype carriers had a significantly longer overall survival time than GG genotype carriers(P=0.007). CASP8-652 6N del/del+del/ins genotype carriers had a significantly shorter progression free survival than ins/ins genotype carriers(P=0.039).After the multi-variants' cox regression analysis,pathological types(P=0.020,RR:2.466, 95%CI:1.150-5.288)and FAS-670 genotype(P=0.036,RR:0.503,95%CI: 0.264-0.955)were found to be independent prognostic factors for these patients.We concluded that polymorphisms in FAS and CASP8 could be predictive or prognostic factors for locally advanced and metastatic NSCLC patients treated with gefitinib. Partâ…¡:Association between Polymorphisms in CYP1A1 and the Clinical Outcome in Advanced Non-Small-Cell Lung Cancer Patients Treated with GefitinibThe variability in treatment response is due to a lot of environmental and genetic factors.In Asia population,polymorphisms in CYP1A1 have been proved to be associated with lung cancer risk.The CYP1A1 genotype was particularly important at a low level of smoking and in the development of squamous cell carcinoma.Since the benefit from gefitinib was also associated with pathological types and smoking status, and gefitinib was metabolized partly by CYP1A1,we investigated the relationship between polymorphisms in CYP1A1 and the clinical benefit and outcome in 88 advanced non-small-cell lung cancer patients treated with gefitinib.We observed that the polymorphisms in CYP1A1 m1 and m2 were not related to the clinical benefit or outcome of these patients.But the subgroup analysis in non-smoking patients showed that CYP1A1 m2 Ile/Ile genotype carriers had a longer overall survival time than Ile/Val + Val/Val genotype carriers(P=0.044).After the multi-variants' cox regression analysis in non-smoking patients,pathological types(P=0.017,RR:2.958,95%CI: 1.215-7.199) and CYP1A1 ml(P=0.016,RR:0.631,95%CI:0.434-0.917) and m2 (P=0.001,RR:4.864,95%CI:1.902-12.441) genotype were found to be independent prognostic factors.So we concluded that polymorphisms in CYP1A1 may be prognostic factors for non-smoking advaced NSCLC patients treated with gefitnib. But since the sample size was small and the interaction between environmental and genetic factors was complicated,it is necessary to do more research work in this field.