Association Study Between Telomere Length And Telomere Related Genes And Esophageal Cancer In Shaanxi Han Population

Background and purpose:The occurrence and development of esophageal cancer(EC)were influenced by genetic and environmental factors.Studies have shown that the genetic background of different individuals can affect the incidence of esophageal cancer,and the difference of this genetic background in the population mainly manifested as single nucleotide polymorphism(SNPs).Telomeres were located at the ends of eukaryotic chromosomes,which ensure the integrity of each chromosome.Telomere length is associated with a variety of diseases.Many studies have shown that the telomere length was regulated by genes.Therefore,the aim of this study was to explore the relationship between telomere length and telomere related gene polymorphisms and the EC risk in Shaanxi Han population,which will provide a profound theoretical basis for the prediction of the risk of esophageal cancer.Methods:This study adopted the case control research strategy,and the subjects of EC patients collected from the First Affiliated Hospital of Xi 'an Jiaotong University in 2017.The controls were collected from the examination center in the same hospital during the same period.The relative telomere length(RTL)of samples were measured by fluorescence realtime quantitative polymerase chain reaction(Q-PCR).The relationship between telomere length and the risk of esophageal cancer was analyzed by mann-whitney U test and multivariate logistic regression analysis.Then,44 SNPs sites of 9 telomere-length related genes were screened through the database.Genotyping of the 44 SNPs were performed using the Agena Mass ARRAY platform.Chi-square test and logistic regression analysis were used to evaluate the correlation between telomere length related gene polymorphism and esophageal cancer's susceptibility in Shaanxi Han population.Results::1.Association analysis of telomere length and risk of EC:The statistical analysis showed that the RTL in the case group was longer than in the controls,and the shorter RTL and longer RTL could increased the risk of EC.2.Association analysis between telomere related genes polymorphisms and genetic susceptibility to EC:(1)In the allele models: The rs10069690,rs2242652 and rs2853676 on the TERT gene are associated with an increased risk of EC.(2)In the genetic models: The ACYP2(rs12615793,rs11896604,and rs17045754),TERT(rs10069690,rs2242652,and rs2853676),and ZNF208(rs2188972,rs2188971,rs8103163,and rs7248488)were significantly associated with increasing the risk of EC.(3)Haplotype analyses revealed that the haplotype “TTCTATG” in the ACYP2 gene was significantly increased the EC risk.The haplotype “TA” and “TG” in the TERT gene and the haplotype “ATAA” in the ZNF208 gene were significantly associated with increasing the risk of EC,respectively.(4)The results of UALCAN database showed that the expressions of ACYP2,TERT and ZNF208 genes were different in cancer tissues and adjacent tissues,as well as in different populations.The effects of high expression and low expression of genes on the survival rate of patients were also different.Conclusions:The results of this study showed that the genetic variation of telomere related genes and the relative telomere length were associated with the risk of esophageal cancer.