Genetic variant of MAML2 in the NOTCH signaling pathway and the risk of bladder cancer
| Autor: | Yang Shen, Zhonglei Deng, Lin Yuan, Hesong Ye, Jingyuan Tang, Long Ma, Qingling Zhang, Qian Lu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
genetic variant China NOTCH pathway Genotype Notch signaling pathway Observational Study Single-nucleotide polymorphism Kaplan-Meier Estimate Polymorphism Single Nucleotide molecular epidemiology single nucleotide polymorphisms 03 medical and health sciences 0302 clinical medicine Risk Factors medicine Humans Genetic Predisposition to Disease 030212 general & internal medicine Allele Bladder cancer business.industry General Medicine medicine.disease Phenotype Introns Urinary Bladder Neoplasms 030220 oncology & carcinogenesis Expression quantitative trait loci ComputingMethodologies_DOCUMENTANDTEXTPROCESSING Trans-Activators Cancer research bladder cancer Biomarker (medicine) Female business Signal Transduction Research Article |
| Zdroj: | Medicine |
| ISSN: | 1536-5964 0025-7974 |
| Popis: | Supplemental Digital Content is available in the text The NOTCH signaling pathway plays a crucial role in cell phenotype and transformation. Single nucleotide polymorphisms (SNPs) may regulate gene expression to trigger bladder cancer susceptibility. Here, we aimed to explore the relationships between genetic variants in the NOTCH pathway and bladder cancer progression. We screened SNPs located in NOTCH pathway genes using the 1000 Genomes Project dataset (CHB). A case-control cohort study including 580 bladder cancer cases and 1101 controls was conducted to genotype the candidate SNPs. The expression quantitative trait locus (eQTL) and bioinformatics analyses were performed to explore the biological function of the SNPs’ host gene and their relationship. Kaplan–Meier analysis was performed to assess the association between host gene expression and bladder cancer patient prognosis. The rs7944701 in the intron of mastermind-like 2 (MAML2) had the strongest signal and was related to bladder cancer risk (OR = 1.329, 95% CI = 1.115–1.583, P = .001). eQTL analysis showed that rs7944701 with a C allele was negatively associated with mastermind-like 2 (MAML2) expression (TT versus TC/CC). Bioinformatics analysis indicated that MAML2expression was lower in bladder cancer tissues than in non-tumor tissues (P = 5.46 × 10−3). Additionally, bladder cancer patients with high MAML2 expression had a significantly poorer prognosis (HR = 1.53, 95% CI = 1.29–1.82, P = .010). The rs7944701 in MAML2 was strongly associated with bladder cancer susceptibility in a Chinese population. This genetic variant and its host gene could be a potential novel biomarker for individuals suffering from bladder cancer. |
| Databáze: | OpenAIRE |
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