Epidemiological evidence for associations between variants in microRNA or biosynthesis genes and lung cancer risk.

Guanchu Liu,Yufu Li,Chunjian Zuo,Jie Tian,Huanwen Chen,Kui Fu

doi:10.1002/cam4.2645

Abstract

In the past decade, the studies involving single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) with lung cancer (LC) risk have been performed, however, these results are inconsistent, and a systematic research synopsis has not been performed yet. Therefore, we attempted to perform comprehensive meta‐analyses to assess the relationships between SNPs in miRNAs or biosynthesis genes and LC risk and further evaluate the epidemiological credibility of these significant associations. We used PubMed, Medline, and Web of Science to search for relevant articles published before 30 May 2019 that assessed relationships between SNPs in miRNAs or biosynthesis genes and LC risk. The cumulative epidemiological evidence of statistical relationships was further assessed combining Venice Criteria and a false‐positive report probability test. Based on 20 publications with 15 969 cases and 17 174 controls, we found that six variants in miRNAs or biosynthesis genes that proved significant associations with LC risk, whereas five proved no association. Subgroup analyses by ethnicity and genetic models were performed, suggesting that four associations were rated as demonstrating strong evidence of relationship with LC risk, including miRNA‐146a rs2910164 in all populations under dominant model and in Asians under dominant and recessive models, and AGO1 rs595961 in Asians under allelic model. Three associations were graded as moderate, and seven associations were rated as weak. This study presents the relationships between SNPs in miRNAs or biosynthesis genes and LC risk, subsequently demonstrates the credibility of these significant associations, and highlights the role in the pathogenesis of LC.

Highlights

Lung cancer (LC), a malignant carcinoma of respiratory system, remains the leading cause of cancer incidence and mortality.[1]
Grade A was assigned to indicate no observable bias, or if bias was unlikely to explain the presence of the association, grade B was assigned if bias could be present, and grade C was allocated if the bias was evident or was likely to explain the presence of the association
For miRNA-499 rs3746444, we found that single nucleotide polymorphisms (SNPs) rs3746444 under dominant model had significant association with LC risk in all populations (OR = 1.142, 95% confidence interval (CI) = 1.0091.294, P = .036), and a nominally significant association between SNP rs3746444 and risk of LC was found in Asians under recessive model (OR = 1.403, 95% CI = 1.034-1.904, P = .029), rather than the allelic or the dominant model, as well as in Caucasians under all three models

Summary

Introduction

Lung cancer (LC), a malignant carcinoma of respiratory system, remains the leading cause of cancer incidence and mortality.[1]. | 1938 exposure and the variations in gene[2]; more than 80% patients with LC have smoked, only less than 20% of smokers will eventually be diagnosed with LC; while nonsmokers with a family history of cancer have a higher LC risk, indicating that variations in gene play a key role in the pathogenesis of LC.[3,4] Many studies involving the relationships between single nucleotide polymorphisms (SNPs) and LC risk had been performed last decade and were taken consideration into as part of the genetic variant study, as well as the role of SNPs in microRNAs (miRNAs), which regulates up to 30% of gene-related human disease.[5,6]. Previous studies have shown that miRNA biosynthesis genes are closely related to the risk of LC, especially AGO1 and GEMIN4.20

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Results

Conclusion