The Investigation of the Association Between the Bcl-2 3’-UTR rs1564483 Polymorphism and miR-296-3p in the Development of Breast and Gastric Cancers

Abstract

Background: B-cell leukemia/lymphoma 2 ( Bcl-2) gene regulates carcinogenesis by inhibiting apoptosis. This study evaluated the association of Bcl-2 3′-untranslated regions (3′ UTR) rs1564483 polymorphism and miR-296-3p with the development of breast and gastric cancers. Methods: A microarray analysis was performed on the Genomic Spatial Event (GSE)29431 and GSE161533 datasets for breast and gastric cancers. Blood samples were taken from 222 (111 patients and 111 controls) and 210 (84 patients and 126 controls) individuals for breast and gastric cancers, respectively. Genomic DNA was extracted from the blood samples and genotyping was performed using real-time polymerase chain reaction (RT-PCR), followed by examining the high-temperature melting curve. Statistical analysis was conducted to examine the potential correlation between the rs1564483 polymorphism and the risk of breast and gastric cancers concerning pathological characteristics. Results: The results of the microarray showed that the Bcl-2 gene was up-regulated in gastric cancer (logFC [log fold change]: 0.65, adjusted P < .05). Clinical outcome showed no notable relationship between the rs1564483 polymorphism and breast cancer risk; however, for gastric cancer, it identified a large difference between healthy controls and patients for an allelic frequency of rs1564483 ( P ⩽ .001). Moreover, an assay of different models (dominant, recessive, and co-dominant) showed a significant association between the AG genotype between control and gastric cases (Pearson chi-square test, P = .046). In addition, the prevalence of the AG genotype was greater in persons under the age of 45 and in patients with H. pylori infection ( P ⩽ .001). The AG genotype was not related to smoking, although the AA genotype was associated with increased cancer incidence in smokers ( P ⩽ .001). Conclusions: In silico studies and calculations of the ΔG binding of micro ribonucleic acid (miRNA) hsa-miR-296-3p to the mutant and wild alleles of the rs15644833 single nucleotide polymorphism (SNP) have revealed that Bcl-2 mRNA expression in gastric cancer decreases, thus confirming the tumor suppressor role of the Bcl-2 gene.