Prognostic role of apoptosis-related gene functional variants in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

Abstract

BackgroundSingle-nucleotide polymorphisms in apoptosis-related genes have been shown to play a role in the efficacy of platinum-based chemotherapy and may influence clinical outcomes. Our study aimed to evaluate the correlations of four functional single-nucleotide polymorphisms − FAS −670 A>G, FAS ligand −844 T>C, survivin −31 G>C, and survivin 9386 C>T – with drug response and clinical outcomes in advanced non-small-cell lung cancer patients who received platinum-based chemotherapy.Materials and methodsPolymorphisms were evaluated using the polymerase chain reaction-based restriction fragment-length polymorphism technique.ResultsPatients with the CC genotype of FAS −670 A>G had worse overall survival (OS) than those with the CT or TT genotype (P=0.044), with median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively. Furthermore, progression-free survival was associated with the FAS −670 A>G polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of survivin 9386 C>T experienced improved survival compared with patients with the TT genotype (median OS 31.4 months and 22.8 months, respectively).ConclusionThe functional FAS −670 A>G and survivin 9386 C>T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy.

FAS and FASL genetic polymorphisms impact on clinical outcome of malignant pleural mesothelioma

“…Finally the results did not show any association between the investigated polymorphisms and response rate which is consistent with the results shown by Tao et al15 However, Liu et al demonstrated that FASL-844 C>T polymorphism has an influence on NSCLC response to platinum agents 24. However, their conclusion is based on the interaction between this polymorphism and other genetic polymorphisms which is contrary to our study and Tao et al hypothesis where the effect of this polymorphism was studied solely and not as interaction with other genetic polymorphisms.…”

“…Previously, Tao et al did not find any relationship between this polymorphism and PFS or OS in Chinese NSCLC patients 15. Also, these results were consistent with Park et al and Wu et al who did not observe a prognostic relevance for this polymorphism in Korean and Chinese NSCLC patients, respectively 17,23…”

“…These findings are consistent with Wu et al but contradictory to Park et al and Tao et al who associated this polymorphism with survival in NSCLC patients 15,17,23. This discrepancy in the results could be attributed to the difference in the studied ethnicities or the difference in studied cancer or may be due to small sample size in our study which may obscure a significant relationship between this polymorphism and prognosis.…”

“…Several studies have investigated the association of these polymorphisms with the prediction of clinical outcome and prognosis in non-small cell lung cancer (NSCLC) and breast and bladder cancers 15–19. However, the results of these studies are nonconclusive.…”

Association between survivin genetic polymorphisms and epidermal growth factor receptor mutation in non-small-cell lung cancer

“…For example, Javid et al found that survivin -31C/C in lung cancer patients was associated with a poor overall survival rate 41, and Rosato et al showed that the -31 C/C genotype was related to node metastasis and patient survival 36. Moreover, Tao et al showed that survivin 9386 C>T polymorphisms are potential independent prognostic factors in NSCLC patients treated with platinum-based chemotherapy 42. The present study showed that survivin -31C/C was stage-related in patients with EGFR exon 19 mutations.…”