Studies Of EYA2 Gene Polymorphisms On Risk Of Non-small-cell Lung Cancer In Yunnan Han Population

Background:Lung cancer is the main cause of cancer death in the world,approximately 80%of patients are diagnosed with non-small-cell lung cancer(NSCLC)in lung cancer patients.The eyes absent homologue 2(EYA2)is a dual-functional transcription factor that was involved in the cellular signal transduction through its phosphatase activity and plays a critical role in multi-organ development.Studies have proved that abnormal expression of EYA2 can promote the proliferation,migration and invasion of multiple cancer cells.EYA2 gene was included in the cancer susceptibility candidate gene.In this study,we analyzed the association between SNPs polymorphisms of the EYA2 gene and non-small-cell lung cancer in Han population of Yunnan province.This study aimed to explore the pathogenesis of non-small-cell lung cancer,and to provide clues for the clinical prevention and treatment of this disease.Methods:Nine SNPs were genotyped in Yunnan Han(case=291,control=384)populations by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and direct sequencing techniques.The statistical analysis was carried out by the computing software of SPSS 16.0,Haplo(?)w4.1,SHEsis and phase.Result:1.The single site analyses indicated that in Yunnan Han populations the frequencies of the C allele of rs6066146(odds ratio[OR]=1.668,95%confidence interval[CI]=1.322-2.104,P＝1.58×10-5)significantly increased the risk of NSCLC,but the frequencies of the T allele of rs13041611(odds ratio[OR]=0.293,95%confidence interval[CI]=0.198-0.432,P=5.89×10-10)significantly decreased the risk of NSCLC.2.Results of stratifed analyses by clinicopathological features revealed that the polymorphism of rs6066146 and rs13041611 did not show any differences among the clinical TNM stage,whereas there was significantly associated with histological classification;Compared with squamous cell carcinoma(SCC),the risk of the rs6066146 and rs13041611 were significantly existed in the patient groups with adenocarcinoma(ADC)(P<0.05).3.The haplotype analyses indicated that four haplotypes were significantly associated with NSCLC,H6(T T G C C C),H7(T T G C T C),H10(T C G C T C)haplotypes increased the risk of NSCLC in Yunnan Han populations;whereas H5(C C A T C T)decreased the risk.Conclusion:Our results demonstrated that C allele of rs6066146 of EYA2 gene was risk factor with NSCLC in Yunnan Han populations.However,T allele of rs13041611 of EYA2 gene was protective factor.Therefore,these two loci might be susceptibility makers of non-small cell lung cancer.