Genetic Variants in the Wnt/β-Catenin Signaling Pathway as Indicators of Bladder Cancer Risk

Abstract

Purpose The genetic factors that influence bladder cancer risk remain largely unknown. Previous research has suggested that there is a strong genetic component underlying the risk of developing bladder cancer. The Wnt/β-catenin signaling pathway is a key modulator of cellular proliferation through its regulation of stem cell homeostasis. Furthermore, variants in the Wnt/β-catenin signaling pathway have been implicated in the development of other cancers leading us to believe this pathway may play a vital role in bladder cancer development. Materials and Methods A total of 230 SNPS in 40 genes in the Wnt/β-catenin signaling pathway were genotyped in 803 bladder cancer cases and 803 healthy controls. Results Twenty SNPs were nominally significant for risk. Individuals with two variants of LRP6: rs10743980 were associated with a decreased risk of bladder cancer (OR=0.76, 95% CI: 0.58–0.99, P=0.039) in the recessive model in the initial analysis and was also validated using the bladder GWAS chip (OR=0.51, 95% CI: 0.27–1.00, P=0.049) (P value for combined analysis: P=0.007). Conclusion Together, these findings implicate variants in the Wnt/β-catenin stem-cell pathway as playing a role in bladder cancer etiology.

Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer

“…In BC tissues, mutations or genetic changes in the regulatory pathway of Wnt/β-catenin signaling resulted in EMT, the emergence of urothelial CSC phenotype, chemoresistance, enhanced survival, and the promotion of tumorigenesis [79]. In urothelial CSCs, the genotyping of single nucleotide polymorphisms of 40 genes in the Wnt/β-catenin signaling pathway revealed variants in the Wnt/β-catenin stem cell pathway that were proven to have a role in the pathogenesis of BC [80]. Another report also showed that the accumulation of β-catenin and dysregulation of the Wnt/β-catenin pathway induced neoplastic proliferation and increased the potential of invasion in BC [81].…”

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

“…The core regulatory factors of endometrial cancer and pancreatic cancer have quite a lot of crosstalk and overlap. Take β -catenin as an example, β -catenin has been revealed to participate in the Wnt signaling pathway in various tumor subtypes [55, 56]. The initiation and progression of both pancreatic cancer and endometrial cancer have been confirmed to be associated with Wnt signaling pathway, implying that such two regulatory networks may have crosstalk and our extracted KEGG pathway (hsa05213) may actually contribute to the progression of pancreatic cancer [57–59].…”

The role of ZBTB38 in promoting migration and invasive growth of bladder cancer cells

“…The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, is closely associated with malignant transformation of cancer cells and metastasis (21,22). In addition, the Wnt/β-catenin pathway has been demonstrated to be involved in the development of bladder cancer (23). The present study aimed to investigate whether ZBTB38 can promote the migration and invasive growth of bladder cancer cells, and to identify the possible effects of ZBTB38 on the Wnt/β-catenin signaling pathway.…”