Association of MiRNA-499 Rs3746444 A>G Variants with Adenocarcinoma of Esophagogastric Junction (AEG) Risk and Lymph Node Status

Background: MicroRNAs (miRNAs) miRNA-499 rs3746444 A>G polymorphism may be complicated in the susceptibility to cancer. However, the correlation of this polymorphism with adenocarcinoma of esophagogastric junction (AEG) was unknown.

Patients And Methods: A total of 1063 AEG patients and 1677 controls were included in this study to assess the association of miR-499 rs3746444 A>G with AEG risk. SNPscan genotyping assay was harnessed to obtain the genotypes of miRNA-499 rs3746444 A>G polymorphism.

Results: We identified that SNP miR-499 rs3746444 A>G increased the susceptibility of AEG (AG vs AA: adjusted OR=1.25, 95% CI=1.05-1.49, =0.012 and AG/GG vs AA: adjusted OR=1.30, 95% CI=1.10-1.54, =0.002). In a stratified analysis, we found that miR-499 rs3746444 A>G polymorphism had an increased susceptibility of AEG in several subgroups (male subgroup: AG vs AA: adjusted =0.004 and AG/GG vs AA: adjusted =0.002; female subgroup: GG vs AG/AA: adjusted =0.046; <64 years subgroup: AG vs AA: adjusted =0.006 and AG/GG vs AA: adjusted =0.003; never smoking subgroup: AG vs AA: adjusted =0.003 and AG/GG vs AA: adjusted =0.001; and never drinking subgroup: AG vs AA: adjusted =0.008 and AG/GG vs AA: adjusted =0.002). The results of power calculation indicated that miR-499 rs3746444 A>G polymorphism increased the risk of AEG in overall comparison, male, <64 years, never smoking, and never drinking subgroups. Among the AEG cases, 625 patients accompanied by positive lymph node. However, the distribution of miRNA-499 rs3746444 A>G variants was no significant difference between different lymph node status.

Conclusion: Our findings indicate that miR-499 rs3746444 A>G polymorphism is significantly associated with AEG susceptibility. In the future, further exploration of this genetic factor in relation to AEG susceptibility with an adequate methodological quality is needed.