Association Between MicroRNA-146a Rs2910164 Single Nucleotide Polymorphism And Susceptibility To Lung Cancer

Objective: Cancer is a major public health problem in most countries and regions of the world,seriously affecting human life and health.Years of research have shown that most of cancers are caused by a variety of environmental carcinogenic factors and individual genetic factors which interact for a long time.Smoking factors are environmental risk factors for a variety of cancers.MicroRNAs,as non-coding micro RNAs,particaipate in tumor occurrence and development.Various researches demonstrated that heritable variation plays a vital role in carcinoma progression.The most common variation is SNP,which affects the expression level of microRNAs to influence the risk of carcinoma.The microRNA-146 a,located on the LOC285628 gene of human chromosome 5,expresses in more than 20 human tissues and organs.The single nucleotide polymorphism of the rs2910164 C/G,located in the stem-loop structure of Pre-microRNA-146 a,affects the expression level of microRNA-146 a,which leading to the dysregulation of microRNA-146 a expression and eventually causes diseases.According to the background,this study aims to investigate the role of microRNA-146 a in cancer by exploring the relationship between microRNA-146 a rs2910164 single nucleotide polymorphism and common cancer susceptibility.And provide a certain theoretical basis for the prevention of cancer in China in the future.Methods: This study through the Meta-analysis to screen out the cancer species,which are associated with the SNP of microRNA-146 a rs2910164.A case-control study was conducted to investigate the effect of polymorphisms on the risk of cancer in smoking populations in northeastern China.1.Methods for Meta-analysisRelevant literature was searched in the PubMed database by using a search strategy for a Meta-analysis,and the case-control studies are conform to the inclusion exclusion criteria.The association between the microRNA-146 a rs2910164 single nucleotide polymorphism and cancer susceptibility was reflected by the OR(Odds ratio)value and its 95% confidence interval.Subgroup analysis was performed by the cancer type,ethnicity,and control population.Sensitivity analysis,Egger’s regression test and Begg’s funnel plot were used to assess the stability of the results.2.Methods of case-control studyThe Meta-analysis was used to screen out the cancer species.The case-control study was designed,and it was approved by the institutional review board of China Medical University and written informed consents were obtained from all people.Basic data and clinical information of the subjects were collected through questionnaires,then we collected the venous blood,extracted the DNA and performed genotyping.The OR value and 95% confidence interval were used to evaluate the relationship between the polymorphism of microRNA-146 a rs2910164 and the cancer susceptibility in the smoking population in Northeast China.Results:1.Results of the Meta-analysisThere was a total of 34,905 individual in the study,including 14670 cases and 20235 controls.And the SNP of microRNA-146 a rs2910164 can be divided into five models,including homozygous genetic model(CC vs GG),heterozygous genetic model(CG vs GG),dominant genetic model(CC + CG vs GG),recessive genetic model(CC vs CG + GG)and allelic genetic model(C vs G).However,the microRNA-146 a rs2910164 polymorphism was not associated with cancer susceptibility in all genetic models.However,in the subgroup analysis,the polymorphism of microRNA-146 a rs2910164 was associated with the susceptibility of lung cancer and nasopharyngeal carcinoma,but was not associated with hepatocellular carcinoma and gastric cancer.No significant association was found in the subgroup analysis of racial and control source.2.Results of case-control studiesAccording to the results of Meta-analysis,we conducted a case-control studies of lung cancer,and 710 subjects were obtained,including 348 cases and 362 controls.The frequency of microRNA-146 a rs2910164 C/G site genotype in the case group was GG 19.54%,CG 51.44%,CC 29.02% and in the control group was GG 20.17%,CG 50.83%,CC 29.00%,and the distribution frequency of each genotype was consistent with HWE balance(P=0.640).There was no significant association between the polymorphism of microRNA-146 a rs2910164 and the risk of lung cancer in smokers in Northeast China.However,in the subgroup analysis,the polymorphism was associated with the susceptibility to lung adenocarcinoma(OR:1.69,95%CI:1.01~2.81,P=0.044),and the C allele might be a risk factor for lung adenocarcinoma.Conclusion: The result of Meta that single nucleotide polymorphism of the microRNA-146 a rs2910164 is associated with the susceptibility of lung cancer and nasopharyngeal carcinoma.And the case-control study show that polymorphisms maybe associated with the risk of lung adenocarcinoma in smokers,and the C allele may be a risk factor.