Abstract
We aimed to explore the associations of polymorphisms in three microRNAs (miRNAs) (let-7e rs8111742, miR-365b rs121224 and miR-4795 rs1002765) that target PGC with the risk and prognosis of gastric cancer/atrophic gastritis. Sequenom’s MassArray was used to genotype the miRNA polymorphisms in 724 gastric cancer cases, 862 atrophic gastritis cases and 862 controls in a Chinese population. We found that let-7e rs8111742 and miR-4795 rs1002765 were associated with the risk of gastric cancer in the H. pylori-positive subgroup. MiR-365b rs121224 was associated with the risk of intestinal-type gastric cancer in the alcohol consumption subgroup. Intestinal-type gastric cancer patients at Borrmann stages III-IV who carry the miR-365b rs121224 GG genotype had better prognosis compared with those who carry the CG or CC genotypes. MiR-365b rs121224 was associated with Lauren typing and TNM staging, in which the distribution of GG genotype carriers in intestinal-type gastric cancer and the TNM stage I-II subgroup was higher than that of CG or CC genotypes, which contrasted with the distribution in diffuse-type gastric cancer or TNM III-IV groups. These findings suggested that the polymorphisms in these miRNAs might be biomarkers for gastric cancer risk and prognosis, especially for populations infected with Helicobacter pylori or who consume alcohol.
Highlights
Genes and multiple miRNAs can be regulated by the same target gene
This paper explored the associations of polymorphisms in three miRNAs that target PGC with the risk and prognosis of gastric cancer and atrophic gastritis
Overall risk analysis revealed that there was no significant correlation between the three miRNA polymorphisms and gastric cancer or atrophic gastritis
Summary
Genes and multiple miRNAs can be regulated by the same target gene. The exploration of the relationship between targeted gene-based miRNA polymorphisms and cancer would be helpful to discover the potential of miRNA target gene-related diseases. Downregulation of PGC in atrophic gastritis or gastric cancer; whether they can be used as diagnostic or prognostic markers of gastric cancer; and what are the relationships between miRNA polymorphisms and Helicobacter pylori infection, smoking and alcohol consumption, as well as other gastric cancer environmental factors, remain unclear. This case-control study aimed to explore the relationships between polymorphisms in the PGC-targeting miRNAs, pri-let-7e, pri-miR-365b, pri-miR-4795, with the risk and prognosis of atrophy gastritis and gastric cancer in a northern Chinese population to explore their potential as specific markers of gastric cancer and its precursor. This study could provide a theoretical and experimental basis for further exploration of the genetic variation of these three miRNAs and the dysregulation of their target gene, PGC, in gastric cancer development
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