The miR526b-5p-Related Single Nucleotide Polymorphisms, rs72618599, Located in 3'-UTR of TCF3 Gene, is Associated with the Risk of Breast and Gastric Cancers

Single nucleotide polymorphisms result in dysregulation of the proto-oncogene TCF3 gene, which is associated with the development, metastasis, and chemoresistance of different malignancies.

GSE10810 microarray dataset and GEPIA2 online software were used to find differentially expressed genes and the TCF3 status in BC and GC, respectively. Plots and figures of microarray analysis were prepared by ggplot2 and pheatmap packages. Differentially expressed genes were obtained by the Bioconductor limma package. In silico analysis was used to predict the functions of rs72618599. BC (n = 123), GC (n = 132) and healthy age and gender matched controls (n = 184) were genotyped, using the high-resolution melting technique.

Based on the allelic comparison study, C allele of rs72618599 was associated with the BC tumor stage IV (66.1%, 78/120, p < 0.0001) and grade III (52.4%, 55/72, p < 0.0001), while the T allele was associated with metastasis (84.2%, 10/162, p < 0.0001). However, in GC patients, the C allele was significantly correlated with H. pylori infection (51.7%, 30/58, p = 0.008), stage III of primary tumors (47.7%, 62/88, p=0.017), stage II of lymph node status (35.5%, 44/74, p = 0.017), and metastasis (52.9%, 90/132, p = 0.044). In silico analysis predicted that rs72618599 leads to the creation of a binding site for hsa-miR526b-5p in the 3′-UTR of TCF3 transcript.

Regarding the rs72618599 SNP, the C allele, is associated with poor prognosis of BC and GC. Furthermore, rs72618599 may be associated with cancer progression by altering the regulatory affinity of hsa-miR526b-5p to 3′-UTR of TCF3.