Study On The Relationship Between The Genetic Polymorphisms Of EIF3a And Susceptibility Of Lung Cancer Development And Clinical Sensitivity To Platinum-based Chemotherapy In Patients With Lung Cancer

Background: Eukaryotic initiation factor 3a (eIF3a) has been thought to play a regulatory role in cell transcription and translations. High expression of eIF3a protein has been found in the tissues of lung cancer. The changes of expression level of genes and gene mutation are probably associated with overall survival rate and the sensitivity of chemotherapy response in cancer patients.Aims: The aims of this study were to explore the novel single nucleotide polymorphisms (SNPs) in eIF3a genes and investigate the association of genetic polymorphisms of these novel SNPs with the susceptibility of lung cancer development and clinical responses to Platinum-based chemotherapy in patients with lung cancer.Methods: We screened 50 DNAs samples in order to looking for some novel SNPs in eIF3a genes from Chinese healthy individuals by direct sequencing. Blood samples in all subjects were collected from the Xiangya hospital of Central South University. The hemi-nested polymerase chain reaction restrition fragment length polymophism (PCR-RFLP) was used to examine G/A polymorphism in exon16 and rs967185(G>A) of eIF3a gene, Pyrosequencing was used to examine rs431898(G>C) polymorphism. We investigated the association of genetic polymorphisms of these SNPs with the susceptibility of lung cancer development and clinical responses to Platinum-based chemotherapy in patients with lung cancer.Results: In this study we screened 20 SNPs in eIF3a gene including 3 SNPs in exons, 2 in 5-UTR, and 15 in introns by direct sequencing. Among of these SNPs, we for the first time found the 4 novel SNPs in eIF3a gene(l 1279 G>A at intron 6, 1458C>T at exon 9, 29671G>A at intron 15,2554G>A at exon 16). The results showed that the frequencies of GG, GA, and AA genotypes in eIF3a gene 2554G>A mutant were 78.8%, 20.6%, and 0.6% in patients with lung cancer, respectively, and 72.9% ,23.5%, and 3.5% in healthy controls, respectively. After a balance in age (in years), sex, and smoking status of all subjects, unconditional logistic regression analysis showed that GA, AA, GA+AA genotype was associated with a decreased risk in the development of lung cancer. In patients with small cell lung cancer, 2554 GA genotypic individuals had better chemotherapy response compared with 2554 GG genotype. In non-small cell lung cancer patients with 2554 GG genotype also had better chemotherapy response compared with 2554 GA genotype.We did not find rs967185(G>A) and rs431898 (G>C) mutants in lung cancer patientsConclusion: The genetic polymorphism of novel 2554G>A mutant in eIF3a gene was not associated with the development of lung cancer. In patients with small cell lung cancer or non small cell lung cancer, different 2554G>A genotyped individuals had different chemotherapy response to platinum-based medicines.