Associations Between SNPs In PVT1 And Lung Cancer Susceptibility

Objective: Lung cancer is a kind of malignant tumor with high invasiveness,high metastasis and high heterogeneity.In China and the world,the morbidity and mortality rate of lung cancer rank first among cancer patients,which has brought serious disease burden in China.Therefore,China needs to pay more attention to the prevention of lung cancer,using scientific and effective methods to explore the pathogenesis of lung cancer,early diagnosis and treatment,improving the prognosis.A large number of epidemiological data show that the key factors of lung cancer susceptibility are environmental factor and genetic factor.Long non-coding RNA(lncRNA)PVT1 has been identified to be related to risk of a variety of cancers,such as lung cancer,gastric cancer,pancreatic cancer and follicular lymphoma.Studies have shown that PVT1rs2608053,rs1561927,and rs13254990 polymorphism were associated with the risk of Hodgkin's lymphoma,pancreatic cancer,and follicular lymphoma,respectively.However,the studies on the association between three SNPs in lncRNAs and the susceptibility of lung cancer were few so far.Therefore,this study assessed the association between genetic polymorphisms of PVT1 and the susceptibility to lung cancer as well as gene-environmental interaction.Methods: A hospital-based case–control study,including 515 lung cancer patients and 582 cancer-free controls,was carried out in three hospitals in Shenyang.Genomic DNA samples were extracted from the peripheral blood of the subjects by Phenolchloroform Method.Taqman? real-time fluorescent quantitative PCR method was applied to detect genotypes of the three SNPs(rs2608053,rs1561927,rs13254990).All statistical results were calculated by SPSS 21.0 software.Our study used Student's t test and ?2 test to verify the difference between cases and controls in age,gender and smoking exposure,respectively.Unconditional logistic regression analyses calculated the odds ratios(ORs)and their 95% confidence intervals(CIs)to assess the associations between polymorphisms of rs2608053,rs1561927,rs13254990 and susceptibility to lung cancer.The gene-environment interaction was evaluated by an additive model.Results: There were no statistically significant association between rs2608053 polymorphism in PVT1 and risk of lung cancer in all subjects.The relationship betweenpolymorphism rs13254990 in PVT1 gene and lung adenocarcinoma was significant.Composed with individuals carrying CC genotypes,TT genotype carriers were more likely to develop lung adenocarcinoma(OR=2.095;95%CI=1.084-4.047,P=0.028).In the recessive model,it also showed a statistically significant difference(TT vs CT+CC:OR=2.251,95%CI=1.174-4.318,P=0.015).Compared with individuals carrying homozygous wild genotype AA,individuals with rs1561927 heterozygous mutant genotype AG 1.386-fold increased risk of lung cancer in subgroup age under60(OR=2.386,95%CI =1.043-5.455,P=0.039).In dominant model,compared with individuals carrying homozygous wild genotype AA,individuals with rs1561927 genotype AG/GG 1.464-fold increased risk of lung cancer(OR=2.464,95%CI=1.086-5.593,P=0.031).According to the result of stratified analysis by smoking status,among nonsmokers,individuals carrying genotype CT had a lower risk of lung cancer than those with CC genotype(OR=0.673,95%CI=0.472-0.959,P=0.028).According to the estimate and 95%CI,gene-environment interaction result was not statistically significant between PVT1 SNP and smoking in additive model.Conclusions: The rs2608053,rs1561927 and rs13254990 polymorphisms of PVT1 were not associated with lung cancer risk.According to the result of stratified analysis by pathological type,rs13254990 polymorphism of PVT1 could affect the risk of lung adenocarcinoma.Moreover,the interactions between three polymorphisms and smoking status were not statistically significant.