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J Urol. 2015 Dec;194(6):1771-6. doi: 10.1016/j.juro.2015.07.032. Epub 2015 Jul 11.

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

Author information

1
Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas.
2
Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: xwu@mdanderson.org.

Abstract

PURPOSE:

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 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 that this pathway may have a vital role in bladder cancer development.

MATERIALS AND METHODS:

A total of 230 single nucleotide polymorphisms in 40 genes in the Wnt/β-catenin signaling pathway were genotyped in 803 bladder cancer cases and 803 healthy controls.

RESULTS:

A total of 20 single nucleotide polymorphisms were nominally significant for risk. Individuals with 2 variants of LRP6: rs10743980 were associated with a decreased risk of bladder cancer in the recessive model in the initial analysis (OR 0.76, 95% CI 0.58-0.99, p=0.039). This was validated using the bladder genome-wide association study chip (OR 0.51, 95% CI 0.27-1.00, p=0.049 and for combined analysis p=0.007).

CONCLUSIONS:

Together these findings implicate variants in the Wnt/β-catenin stem cell pathway as having a role in bladder cancer etiology.

KEYWORDS:

Wnt signaling pathway; beta catenin; polymorphism; risk; single nucleotide; urinary bladder neoplasms

PMID:
26173102
PMCID:
PMC5087323
DOI:
10.1016/j.juro.2015.07.032
[Indexed for MEDLINE]
Free PMC Article

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