The Association Between PAX8-AS1 Polymorphism And Susceptibility To Lung Cancer

Objective:Lung cancer is a common malignant tumor in China,which brings a serious disease burden to our country.Therefore,it is particularly imperative to find the environmental and genetic factors of occurrence of lung cancer.A large number of epidemiological investigations have indicated that tobacco exposure is a major environmental risk factor for lung cancer.In addition to environmental risk factors,genetic factors including genetic polymorphisms are the most critical risk factors for occurrence and development of lung cancer.Long non-coding RNA is inseparable from the carcinogenic processes among many types of cancer.PAX8 is overexpressed in non-small cell lung cancer(NSCLC),and speculated that PAX8 is likely to interfere with p53transcription and contribute to the development of tumor.Silencing of PAX8 expression may impair viability and motility of NSCLC cells.This study was the first to explore the relationship between lncRNA PAX8-AS1 rs4848320 and rs1110839 polymorphisms and susceptibility to lung cancer.Methods:1.Experimental methods:This present study was a hospital-based case-control study with 434 patients of lung cancer and 593 normal controls,and collected 5 ml of peripheral venous blood from all included subjects.Then,anticoagulant genomic DNA was extracted by classical phenol-chloroform method.Taqman~?real-time fluorescent quantitative PCR method was applied to detect genotypes of the two SNPs(rs4848320 and rs1110839).2.Statistical analysis methods:First,the t-test,chi-square test and logistic regression analysis were used to compare the differences in age,gender and smoking status between case group and control group.Secondly,logistic regression analysis was used to calculate the OR with its 95%CI to evaluate the relationship between the two rs4848320and rs1110839 loci genotypes and the risk of lung cancer.Finally,the interaction of rs4848320 and rs1110839 polymorphisms with smoking was evaluated.(1)The interaction of two PAX8-AS1 SNPs polymophisms with smoking was evaluated by cross-analysis.(2)The additive model interaction of two PAX8-AS1 SNPs polymophisms with smoking was evaluated by relative excess risk due to interaction(RERI),synergy index(S)and attributable proportion due to interaction(AP).All statistical analysis in this paper is performed using SPSS20.0 software.Results:There were no statistically significant associations between rs4848320 and rs1110839 polymorphisms in PAX8-AS1 and risk of lung cancer.However,in the smoking subgroup,we found that individuals carrying the rs4848320 CT+TT genotype 0.929-fold increased risk of lung cancer compared to individuals with the homozygous wild genotype CC(OR=1.929,95%CI=1.070-3.479,P=0.029).Compared with individuals carrying the C allele,individuals with rs4848320 T allele 0.966-fold increased risk of lung cancer(T vs.C:OR=1.966,95%CI=1.185-3.261,P=0.008).Compared with individuals carrying homozygous wild genotype TT,individuals with rs1110839 homozygous mutant genotype GG 2.224-fold increased risk of lung cancer(OR=3.224,95%CI=1.089-9.544,P=0.034).rs1110839 G allele carriers 0.530-fold increased risk of lung cancer compared with individuals carrying homozygous wild genotype T(G vs.T:OR=1.530,95%CI=1.028-2.278,P=0.036).In male population,rs1110839 genetic variant was related to the risk of lung cancer in all genetic models(GG vs.TT:OR=3.096,95%CI=1.343-7.134,P=0.008;TG+GG vs.TT:OR=1.804,95%CI=1.061-3.067,P=0.029;GG vs.TG+TT:OR=2.376,95%CI=1.102-5.121,P=0.027;G vs.T:OR=1.621,95%CI=1.149-2.287,P=0.006)rather than heterozygous model.Cross-analysis showed that compared with non-smokers carrying homozygous wild-type CC,smokers carrying the rs4848320 CT/TT genotype 1.218-fold increased risk of lung cancer(OR=2.218,95%CI=1.272-3.869,P=0.005).In addition,smokers carrying the rs1110839 TG/GG risk genotype 0.755-fold increased risk of lung cancer compared with non-smokers carrying homozygous wild-type TT(OR=1.755,95%CI=1.108-2.781,P=0.017).However,parameter estimates and their 95%confidence intervals of the additive model interaction provided that no significant additive model interaction between rs4848320 and rs1110839 polymorphisms and smoking exposure on risk of lung cancer.Conclusions:The rs4848320 and rs1110839 polymorphisms of PAX8-AS1 were not associated with lung cancer risk.However,in smoking and male subgroup,PAX8-AS1rs4848320 and rs1110839 polymorphisms may be associated with lung cancer susceptibility.