The correlation ofmicroRNA-499rs3746444 T>C locus with the susceptibility of gastric cancer: from a case–control study to a meta-analysis

Abstract

The relationship between rs3746444 T>C single-nucleotide polymorphism (SNP) in microRNA (mir)-499 and risk of gastric cancer (GC) has been widely investigated. However, the association was still unconfirmed. Here, we first recruited 490 GC patients and 1476 controls, and conducted a case-control study. And we did not find any association between rs3746444 T>C SNP polymorphism and risk of GC. Subsequently, we conducted a meta-analysis to explore the association of mir-499 rs3746444 polymorphism with GC development. Two authors searched the PubMed and EMBASE databases up to October 15, 2019 independently. Finally, nine literatures involving 12 independent studies were included. In total, 3954 GC cases and 9745 controls were recruited for meta-analysis. The results suggested that allele model, homozygote model and recessive model could increase the risk of overall GC (P = 0.002, 0.009 and 0.013, respectively). When we excluded the studies violated HWE, this association was also found in allele model (P = 0.020) and dominant model (P= 0.044). In subgroup analyses, we identified that rs3746444 SNP in mir-499 increased the risk of GC in Asians and gastric cardiac adenocarcinoma (GCA) subgroups. No significant bias of selection was found (all P>0.1). Test of sensitivity analysis indicated that our findings were stable. Additionally, we found that the power value was 0.891 in the allele model, suggesting the reliability of our findings. In summary, our analysis confirmed the association between rs3746444 and the risk of GC, especially in Asians and in patients with GCA.

Functional gene polymorphisms and expression alteration of selected microRNAs and the risk of various gastric lesions in Helicobacter pylori-related gastric diseases

“…Another study reported that although there was no significant association between miR-27a rs895819 and gastrointestinal tumor risk, this SNP could synergize with other risk factors to increase the risk of gastrointestinal tumors ( Shankaran et al, 2020 ). Meanwhile, several studies have found that there are different degrees of associations between miR-499 rs3746444, miR-149 rs2292832, miR-146a rs2910164 and GC risk ( Zhang et al, 2018 ; Rong et al, 2021 ; Liang et al, 2022 ). And as we know, the occurrence and development of many diseases is a complex processes involving multifactor, multigene and multistage.…”

“…Frontiers in Genetics frontiersin.org (Zhang et al, 2018;Rong et al, 2021;Liang et al, 2022). And as we know, the occurrence and development of many diseases is a complex processes involving multifactor, multigene and multistage.…”

The Role and Interactions of Programmed Cell Death 4 and its Regulation by microRNA in Transformed Cells of the Gastrointestinal Tract

“…The association of miRNA-499 with cancers of the GI tract has concentrated on examining the relationship between Single nucleotide polymorphisms (SNPs) in miRNA-499 rs3746444 and susceptibility to GI tract tumorigenesis. Investigators have found that specific polymorphisms can increase the risk of ESCC ( 244 ), GC ( 245 ) and CRC ( 246 ) or have no effect on GI cancer susceptibility ( 247 , 248 ).…”

Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population

“…In addition, various research groups have been analyzing the role of genetic polymorphisms of miRNAs in GC under the rationale of hypothesis-driven (candidate gene) approach [ 15 ]. These studies, mostly conducted in Asia, evidenced the role of miRNA and its polymorphisms as potential new targets for diagnosis and treatment of GC [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Unfortunately, in the Latin American population, in particular in the Chilean population which has one of the highest GC mortality rates [ 1 , 2 , 3 ], no studies have been conducted in this area.…”

“…Therefore, we analyzed all genetic polymorphisms of miRNAs deposited in miRBase, including those which have already been evaluated in other studies [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Here, we identified seven previously unreported genetic polymorphisms: rs4822739 in miR-548j, rs701213 in miR-4427, rs15538677 in miR-4274, rs12416605 in miR-938, rs1439619 in miR-3175, rs61449511 in miR-6891, rs404337 in miR-8084, and rs7500280 in miR-4719.…”