Study On The Relationship Between PRNCR1 Polymorphisms And Lung Cancer Susceptibility In Chinese Northeast Population

Objective:As one of the most common malignancies worldwide,lung cancer is the leading cause of cancer morbidity and death in both men and women.Moreover,lung cancer is also considered as a major public health problem that deserves great attention from researchers and needs further study in today’s China,which has brought great pressure and burden to the social and economic development of our country.Related studies showed that lung cancer was affected by both genetic factors and environmental factors.In addition,studies have reported that many single nucleotide polymorphisms（SNPs）in long non-coding RNA（lnc RNA）genes were closely related to the occurrence of cancer.PRNCR1 could competitively bind mi R-448 to up-regulate HEY2 to achieve the important goal of promoting the research and progress of non-small cell lung cancer（NSCLC）.Several studies have confirmed that PRNCR1 rs13252298,rs1016343,and rs1456315 polymorphisms were associated with the risk of multiple cancers.Based on the role of PRNCR1 in the occurrence and development of lung cancer and the regulation of SNPs on the expression of lnc RNA genes,this study speculated that SNPs in PRNCR1 might affect the risk of lung cancer.Therefore,the purpose of this study was to explore the relationship between PRNCR1 gene polymorphisms and lung cancer susceptibility.Methods:1.Research methods:This study was a classical hospital-based case-control study.According to the inclusion and exclusion criteria formulated in advance,a total of 576 lung cancer cases and 612 healthy controls were included as the research objects.An epidemiological investigation was conducted on the subjects,which included collecting background information on their age,gender,and smoking exposure,and then,every subject donated approximately 5 m L of venous blood.In this study,anticoagulant genomic DNA was extracted from venous blood of all subjects using classical phenol-chloroform method.Then three variants（rs13252298,rs1016343,and rs1456315）were genotyped using Taqman^?real-time fluorescent quantitative PCR method.The potential function of the candidate SNPs in PRNCR1 gene were predicted using the Haplo Regv4.1 database.2.Statistical analysis methods:First,this study used the Student’s t-test andχ² test to analyze the differences in age,gender,and smoking status between the lung cancer case group and the control group.Second,the goodness-of-fitχ² test was used to evaluate whether each genotype in the control group meets Hardy-Weinberg equilibrium.Logistic regression analysis was used to evaluate the association of three SNPs with lung cancer susceptibility.The linear-by-linear association ofχ² test was conducted to calculate cumulative effects of risk alleles.Finally,the interaction between PRNCR1 SNPs and smoking exposure was calculated using crossover analysis.The additive model interaction between PRNCR1 SNPs and smoking was evaluated by using relative excess risk due to interaction（RERI）,attributable proportion due to interaction（AP）,and synergy index（S）.The statistical analysis software used in this study was SPSS 25.0.Results:Compared with individuals carrying rs13252298 homozygous wild AA genotype,individuals carrying GG genotype had a significantly increased risk of lung cancer（OR=1.565,95%CI=1.091-2.245,P=0.015）.Compared with individuals carrying the rs13252298 homozygous wild AA and heterozygous AG genotypes,individuals carrying the homozygous mutant GG genotype 0.719-fold increased risk of lung cancer（OR=1.719,95%CI=1.226-2.410,P=0.002）.Taking individuals with rs1456315 AA genotype as a reference,individuals with GG genotype have a high risk of lung cancer（OR=1.488,95%CI=1.015-2.180,P=0.042）.The results of the recessive model showed that individuals carrying the homozygous mutant GG genotype of rs1456315 are 0.484-fold increased risk of lung cancer than those carrying the AA and AG genotypes（OR=1.484,95%CI=1.032-2.134,P=0.033）.This study showed that rs13252298 and rs1456315 polymorphisms of PRNCR1 were related to the susceptibility to lung cancer and its subtypes,but did not find that rs1016343 variant was statistically associated with the susceptibility to lung cancer and its subtypes.Results of crossover analysis showed that compared with non-smokers carrying the rs13252298 AG and AA genotypes,smokers who carried the homozygous GG genotype had a 1.830-fold increased risk of lung cancer（OR=2.830,95%CI=1.581-5.065,P<0.001）.Compared with non-smokers carrying wild homozygous rs1456315 AA genotype,smokers carrying AG and GG genotypes had a 1.604 times higher risk of lung cancer（OR=2.604,95%CI=1.809-3.750,P<0.001）.The results of the additive model interaction showed that rs13252298 and rs1456315 variants and smoking exposure have no significant additive model interaction on the risk of lung cancer.Conclusions:In this study,the rs13252298 GG genotype and rs1456315 GG genotype in PRNCR1 could increase the risk of lung cancer in the population in northeast China,and they are genetic susceptibility factors of lung cancer.The results of stratified analysis showed that rs13252298 GG genotype and rs1456315 GG genotype were associated with increased susceptibility to non-small cell lung cancer and lung adenocarcinoma.The rs13252298 G allele was an increased risk factor for lung adenocarcinoma and lung squamous cell carcinoma.