rs11671784 G/A and rs895819 A/G Polymorphisms Inversely Affect Gastric Cancer Susceptibility and miR-27a Expression in a Chinese Population
Bo Song, Ge Yan, Hankun Hao, Bei Yang
Department of Gastroenterology, Yantai Shan Hospital, Yantai, Shangdong, China (mainland)
Med Sci Monit 2014; 20:2318-2326
rs895819 and rs11671784 are 2 SNPs in miR-27a that can influence the expression of mature miRNA. However, their role in gastric cancer development is still not well understood. This study aimed to determine whether these 2 polymorphisms are associated with gastric cancer risk in a Chinese population and how they influence the expression of miR-27a
Material and Methods: This was a case-control study and recruited 278 gastric cases and 278 healthy matched controls. Genotyping of these 2 SNPs among the participants were performed to assess their association with gastric cancer risk. Tumor samples from 59 patients who had physical resection were used for qRT-PCR analysis of miR-27a expression. To further valid the effects of these 2 SNPs, findings of previous studies were pooled to generate integrated evidence.
Results: Individuals with rs895819 G variants exhibited significantly increased risk of gastric cancer, while subjects with rs11671784 A variants had significantly reduced gastric cancer risk. Among the patients, rs895819 G variants were moderately associated with lymphatic invasion and lymph node metastasis, while rs11671784 A variants were associated with significantly reduced risk of lymphatic invasion. qRT-PCR results demonstrated rs895819 polymorphism contributed to an aberrant process from pri-miR-27a to pre-miR-27a, but rs11671784 did not affect the transcription and post-transcription processes of the miR-27a gene. The subsequent meta-analysis largely confirmed the effects of these 2 SNPs on gastric cancer risk.
Conclusions: rs895819 and rs11671784 inversely affect gastric cancer risk and the influence was closely related to their effects on miR-27a expression.
Keywords: Asian Continental Ancestry Group - genetics, China, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Genetic Predisposition to Disease, MicroRNAs - metabolism, Odds Ratio, Polymorphism, Single Nucleotide - genetics, Risk Factors, Stomach Neoplasms - pathology