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.