Genetic variations in Hippo pathway genes influence bladder cancer risk in a Chinese population
- 2 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Archives of Toxicology
- Vol. 94 (3), 785-794
- https://doi.org/10.1007/s00204-020-02663-z
Abstract
The Hippo pathway participates in development of numerous tumors through regulating tissue growth and cell fate. This study aimed to detect the association between the genetic variants in Hippo pathway genes and bladder cancer risk in a Chinese population. A case–control study of 580 cases and 1101 controls was performed to evaluate the association of single nucleotide polymorphisms (SNPs) in 39 candidate genes involved in the Hippo pathway with bladder cancer risk. A logistic regression model was used to assess the effects of SNPs on bladder cancer susceptibility. Candidate gene expression in human bladder cancer samples was detected using The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) datasets. We found that SNP rs755813 in WWC1 was significantly associated with a decreased risk of bladder cancer [odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.66–0.88, P = 3.63 × 10–4], which was more common in patients with low grade and non-muscle invasive tumors. Younger subjects (age ≤ 65) (OR = 0.70, 95% CI = 0.56–0.86), females (0.35, 0.23–0.52) and non-smokers (0.72, 0.58–0.88) showed a pronounced association between the rs755813 C allele and risk of bladder cancer by stratified analysis. The WWC1 was upregulated in bladder cancer tissues according to TCGA and GEO datasets. These findings indicated that genetic variant of WWC1 gene in Hippo signaling pathway contributes to the decreased risk of bladder cancer in the Chinese population and may have the protective effect against the development of bladder cancer.Keywords
Funding Information
- National Natural Science Foundation of China (81872691)
- Collaborative Innovation Center for Cancer Personalized Medicine, and Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine)
This publication has 34 references indexed in Scilit:
- Genetic variants in Hippo pathway genesYAP1,TEAD1andTEAD4are associated with melanoma-specific survivalInternational Journal of Cancer, 2015
- The emerging roles of YAP and TAZ in cancerNature Reviews Cancer, 2015
- Phosphorylation of KIBRA by the extracellular signal-regulated kinase (ERK)–ribosomal S6 kinase (RSK) cascade modulates cell proliferation and migrationCellular Signalling, 2014
- Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladderBMC Cancer, 2013
- High expression of KIBRA in low atypical protein kinase C‐expressing gastric cancer correlates with lymphatic invasion and poor prognosisCancer Science, 2012
- KIBRA exhibits MST-independent functional regulation of the Hippo signaling pathway in mammalsOncogene, 2012
- KIBRA Regulates Hippo Signaling Activity via Interactions with Large Tumor Suppressor KinasesOnline Journal of Public Health Informatics, 2011
- The Hippo Signaling Pathway in Development and CancerDevelopmental Cell, 2010
- Kibra Functions as a Tumor Suppressor Protein that Regulates Hippo Signaling in Conjunction with Merlin and ExpandedDevelopmental Cell, 2010
- KIBRA Modulates Directional Migration of PodocytesJournal of the American Society of Nephrology, 2008