Abstract
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). 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.