Association Between Long Noncoding RNA MEG3 Polymorphisms And Lung Cancer Susceptibility

Objects: The incidence and mortality of lung cancer in China ranks first among malignant tumors,and the incidence is still increasing year by year.Genetic susceptibility and environmental risk factors have an important impact on the occurrence and development of many chronic diseases,including lung cancer.Long noncoding RNA(lncRNA)Maternal-Expressed Gene 3(MEG3)is associated with proliferation of various tumor cells and has decreased expression in many types of cancers.Single nucleotide polymorphisms(SNPs)may affect the development and progression of cancer by affecting gene expression,and single nucleotide polymorphisms are widely distributed in lncRNA.In this study,we aimed at demonstrating the association between MEG3 polymorphisms and the risk of lung cancer.Methods:According to inclusion and exclusion criteria,there were 526 lung cancer patients and 526 healthy controls included in this hospital-based case-control study.The genotyping of two polymorphisms,rs7158663 G > A and rs4081134 G > A,was performed by the Taqman allelic discrimination method.The distribution differences of variables between cases and controls were compared by chi-square test and t-test.The goodness of fit test was used to calculate the Hardy-Weinberg equilibrium.Logistic regression analysis was used to assess the association between two SNP polymorphisms and the risk of lung cancer.All of the study followed the ethical standards of the Ethics Committee of China Medical University.Results: A total of 1052 participants were included in the study,including 526 cases and 526 controls.In the cases group,there were 424(80.6%)patients with non-small cell lung cancer,74 patients(14.1%)with small cell lung cancer and 28 patients(5.3%)with other types of lung cancer.The genotype frequencies of the two loci in the control group were consistent with the Hardy-Weinberg equilibrium.Logistic regression analysis found that the MEG3 rs4081134-AA genotype may reduce the risk of lung cancer compared with the GG genotype.After adjusting for age,sex and smoking exposure the odds ratio was 0.487(95% CI = 0.255-0.933,P = 0.030).In the recessive model,we found that the rs4081134 AA genotype could significantly reduce the risk of lung cancer compared with the AG or GG genotype.The adjusted odds ratio was 0.522(95% CI = 0.274-0.992,P = 0.047).The difference was statistically significant.After stratification by age,none statistical correlation was observed in all of the age groups.However,it was noteworthy that we observed a borderline significance in the dominant model of the rs4081134 subgroups of age >60(P = 0.055).In the non-exposure smoking group of rs4081134,the patients with the AG genotype had a lower risk of lung cancer,compared with the homozygous GG,OR=0.708(95%CI = 0.505-0.994,P = 0.046).In addition,we did not find the correlation between the MEG3 rs7158663 polymorphism and the risk of lung cancer.We conducted the crossover analysis to evaluate the effects of polymorphisms and smoking interactions on lung cancer susceptibility,and there were no statistical significance was found.Conclusion: MEG3 rs4081134 polymorphism was associated with lung cancer susceptibility in the Chinese population.