Sequence Variations in the MicroRNA Binding Sites at the 3'UTR of the Apoptosis Genes CASP3, CASP6 and CASP7 and Risk of Gastric Cancer: a Parellel Study at Sister Insitutes
Although environmental factors play roles in the gastric cancer etiology, only a fraction of the exposed develop the disease, suggesting a genetic susceptibility in the general population. microRNAs (miRNAs) play a role in regulating apoptosis in cancer by binding to the 3’ untranslated region (UTR) of the mRNAs of their target genes, resulting in either degradation of target messenger RNAs or repression of their translation and leading to down-regulation of the proteins encoded by the mRNAs. It is likely that single nucleotide polymorphisms (SNPs) located in such miRNA binding sites may cause differential mRNA expression, resulting in deregulation of target-gene expression. In this SINF application, we hypothesize that genetic variants in the predicted miRNA-binding sites of caspase genes are associated with abnormal expression of mRNAs in peripheral blood mononuclear cells (PBMCs) and are associated with risk of gastric cancer. We will test our hypothesis by performing a case-control analysis of available biological materials (PBMCs and DNA samples) of 500 cases and 500 cancer-free controls at each of the participating institutions to determine.