Association Between NINJ2 Gene Polymorphysm And Susceptibility To Lung Cancer

Objective:The morbidity and mortality of lung cancer rank in the top among tumors,and its survival rate has not improved significantly in recent years.Smoking is recognized as the most important risk factor for lung cancer,but the occurrence of lung cancer is the result of the interaction between environment and body.NINJ2 is an intercellular adhesion molecule,which can promote the occurrence and development of colorectal cancer,glioblastoma and endometrial cancer.The expression level of NINJ2 in lung cancer is higher than that in normal lung tissue.We speculate that NINJ2 may promote the development of lung cancer.Single nucleotide polymorphism(SNPs)is a common mutation in genes,which can regulate gene expression by changing the affinity of target RNA,affect the splicing,translation,stability of proteins,and amino acid structure and function,and thus affect the susceptibility,metastasis and invasion of tumors.The aim of this study is to analyze the relationship between NINJ2 gene polymorphisms and lung cancer susceptibility in order to enrich the possible gene loci related to lung cancer.Methods:A hospital-derived case-control design was used in this study.A total of 461lung cancer cases and 487 controls were collected according to the established inclusion and exclusion criteria.The clinical information of the subjects was collected through a questionnaire,and 5ml peripheral venous blood was collected for later use.Genomic DNA was extracted using the classical phenol-chloroform method.The alleles of rs12425791and rs118050317 were genotyped by Taq Man genotyping technology.K-S test was used to test the normality of age distribution.Rank-sum test and Pearsonχ~2 test were used to analyze the distribution differences of continuous variables and categorical variables between the case group and the control group,respectively.The goodness-of-fit chi-square test was used to determine whether the distribution of genotypes at the two loci in the control group was in accordance with Hardy-Weinberg equilibrium.Unconditional logistic regression analysis was used to calculate the OR and 95%CI of the two SNPS and the susceptibility to lung cancer.If there was a theoretical frequency less than 1 in the four-grid table,Fisher’s exact probability method was used to test the relationship between SNPs and the susceptibility to lung cancer.The interaction between rs12425791 and rs118050317 genotypes and smoking was analyzed by crossover analysis.Quantitative measures,Relative excess risk due to interaction(RERI),Attributable proportion due to interaction(AP)and Synergy index(S)were used to evaluate the additive model.SPSS25.0(IBM SPSS,Inc.Chicago,IL,USA)software was used for statistical analysis(two-sided test,Alpha=0.05).Result:In this study,we found that NINJ2 rs12425791 polymorphism was associated with lung cancer risk.Compared with the GG genotype,the AG genotype carriers had a reduced risk of lung cancer(OR=0.708,95%CI:0.537-0.932,P=0.014)and squamous cell carcinoma(OR=0.658,95%CI:0.444-0.977,P=0.038).Similar results were obtained when stratified analysis was performed.When stratified by sex,in the male subgroup,rs12425791 AG genotype carriers had a lower risk of lung cancer than GG carriers(OR=0.674,95%CI=0.474-0.959,P=0.028).Compared with GG carriers,AA OR AG carriers had a 28.3%lower risk of lung cancer(OR=0.717,95%CI:0.516-0.997,P=0.048).When stratified by smoking status,rs12425791AG genotype also had a lower risk of lung cancer than GG in the non-smoking subgroup(AGvs.GG:OR=0.677,95%CI=0.470-0.976,P=0.037;AA+AGvs.GG:OR=0.655,95%CI:0.459-0.933,P=0.019;Avs.G:OR=0.731,95%CI=0.547-0.978,P=0.035).When stratified by gender and smoking status,multiple models showed no significant association between rs12325791 polymorphism and lung cancer risk in female non-smokers,female smokers and male smokers(P>0.05).0.05);Compared with GG genotype,rs12425791AA or AG genotype decreased the risk of lung cancer by 45.6%(OR=0.544,95%CI=0.307-0.963,P=0.037)in non-smoking male subgroup.The allele model showed that rs12425791A allele carriers had a significantly lower risk of lung cancer than G allele carriers(OR=0.571,95%CI=0.347-0.937,P=0.027).When stratified by age,there was no significant association between rs12425791 polymorphism and lung cancer risk in multiple models(P>0.05).NINJ2 gene rs118050317 polymorphism is not associated with lung cancer risk.The results of crossover analysis showed that compared with the rs12425791GG genotype and smokers,the risk of lung cancer in the GG genotype and non-smokers was 0.434 times(95%CI:0.300-0.628,P<0.001);AG or AA genotype and non-smokers had a significantly lower risk of lung cancer(OR=0.287,95%CI:0.190-0.432,P<0.001).Smokers with GG genotype of rs118050317 had 2.510 times higher risk of lung cancer than non-smokers(95%CI:1.808-3.485,P<0.001);rs118050317 CG or CC genotype carriers with smoking exposure had a higher risk of lung cancer than GG genotype non-smokers,OR=2.878(95%CI:1.675-4.945,P<0.001).In additive model,there was no significant interaction between rs12425791 and rs118050317 polymorphisms in NINJ2 gene and smoking risk factors(RERI and AP 95%CI both included 0,S both included 1).Conclusion:In this study:AG genotype of rs12425791 in NINJ2 gene had a lower risk of lung cancer than GG genotype,and AG genotype could reduce the risk of lung squamous cell carcinoma.Rs118050317 polymorphism in NINJ2 gene is not associated with lung cancer risk.Results from the crossover analysis showed that rs12425791 and rs118050317might have combined effects with smoking.In additive model,there was no interaction between NINJ2 gene rs12425791 and rs118050317 polymorphisms and smoking risk factors.