Abstract

ObjectiveThe present study investigates the influence of genetic variants in miRNA machinery genes (DROSHA, DICER, AGO1, and GEMIN4) on gastric cancer in Chinese Han population, further revealing the genetic mechanisms of gastric cancer occurrence and development.MethodsGenotyping of single nucleotide polymorphisms (SNPs) was performed in 628 patients with GC and 502 frequency-matched (age and gender) controls by the high resolution melting (HRM) method.ResultsThe SNPs rs3742330 (DICER) and rs7813 (GEMIN4) were associated with susceptibility to gastric cancer (P = 0.002 and 0.010, respectively). Stratified analysis showed that the G allele of rs3742330 and genotype TT as well as T allele of rs7813 were associated with a later stage of gastric cancer (P=0.027, 0.032 and 0.018, respectively). Furthermore, the genotype TT and T allele of rs7813 appeared to be associated with a higher level of lymphatic metastasis of gastric cancer (P=0.021 and 0.030, respectively), while the genotype AA and A allele of rs636832 (AGO1) were correlated with a lower level of lymphatic metastasis of gastric cancer (P=0.016 and 0.041, respectively). There was no significant association between rs10719 (DROSHA) and gastric cancer.ConclusionThe present data demonstrated that genetic variants in miRNA machinery genes had a significant association with GC susceptibility (DICER and GEMIN4) and malignant behavior such as tumor stage (DICER and GEMIN4) and lymphatic metastasis of GC (GEMIN4 and AGO1) in Chinese Han population.

Highlights

  • Association between SNPs in microRNA machinery genes and gastric cancer susceptibility, invasion, and metastasis in Chinese Han population www.impactjournals.com/oncotarget/

  • SNP ID rs642321 rs6877568 rs10719 rs3757 rs720012 rs417309 rs1640299 rs14035 rs3742330 rs595961 rs636832 rs4961280 rs104591 rs104581 rs7813 rs2740349 rs3744741 rs197412 rs1106042 rs10773771

  • Position 3'UTR 5'UTR 3'UTR 3'UTR 3'UTR 3'UTR 3'UTR 3'UTR 3'UTR intron intron promotor 3'UTR Coding exon Coding exon Coding exon Coding exon Coding exon Coding exon 3'UTR

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Summary

Introduction

Association between SNPs in microRNA machinery genes and gastric cancer susceptibility, invasion, and metastasis in Chinese Han population www.impactjournals.com/oncotarget/

Results
Conclusion
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