Pathway analysis of bladder cancer genome-wide association study identifies novel pathways involved in bladder cancer development

Chen, Meng; Rothman, Nathaniel; Ye, Yuanqing; Gu, Jian; Scheet, Paul; Huang, Maosheng; Chang, David W.; Dinney, Colin P.N.; Silverman, Debra T.; Figueroa, Jonine D.; Chanock, Stephen J.; Wu, Xifeng

doi:10.18632/genesandcancer.113

Cited by 12 publications

(7 citation statements)

References 51 publications

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“…GWAS also identified variants in genes involved in many other pathways as well as in yet not-annotated pathways. A recent pathway analysis based on GWAS data further identified variants in 9 novel genes ( RAPGEF1 , SKP1 , HERPUD1 , CACNB2 , CACNA1C , CACNA1S , COL4A2 , SRC , and CACNA1C ) [ 44 ]. Functional analyses have also provided evidences of causality for GSTM1-null, NAT2-slow, APOBEC- rs1014971, CCNE1 -rs8102137, SLC14A1 -rs10775480, PSCA -rs2294008, UGT1A -rs1189203, and TP63 -rs35592567 [ 45–52 ].…”

Section: Discussionmentioning

confidence: 99%

Bladder Cancer Genetic Susceptibility. A Systematic Review

Maturana

Rava

Anumudu

et al. 2018

BLC

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Background:The variant/gene candidate approach to explore bladder cancer (BC) genetic susceptibility has been applied in many studies with significant findings reported. However, results are not always conclusive due to the lack of replication by subsequent studies.Objectives:To identify all epidemiological investigations on the genetic associations with BC risk, to quantify the likely magnitude of the associations by applying metaanalysis methodology and to assess whether there is a potential for publication/reporting bias.Methods:To address our aims, we have catalogued all genetic association studies published in the field of BC risk since 2000. Furthermore, we metaanalysed all polymorphisms with data available from at least three independent case-control studies with subjects of Caucasian origin analyzed under the same mode of inheritance.Results:The characterization of the genetic susceptibility of BC is composed of 28 variants, GWAS contributing most of them. Most of the significant variants associated with BC risk are located in genes belonging to chemical carcinogenesis, DNA repair, and cell cycle pathways. Causal relationship was also provided by functional analysis for GSTM1-null, NAT2-slow, APOBEC-rs1014971, CCNE1-rs8102137, SLC14A1-rs10775480, PSCA-rs2294008, UGT1A-rs1189203, and TP63-rs35592567.Conclusions:Genetic susceptibility of BC is still poorly defined, with GWAS contributing most of the strongest evidence. The systematic review did not provide evidence of further genetic associations. The potential public health translation of the existing knowledge on genetic susceptibility on BC is still limited.

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Section: Discussionmentioning

confidence: 99%

Bladder Cancer Genetic Susceptibility. A Systematic Review

Maturana

Rava

Anumudu

et al. 2018

BLC

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“…In line with previously published articles, CACNA1C was up-regulated in brain tumors, leukemia, breast cancer and other tumors [ 14 ]. Besides, variants of CACNA1C were associated with bladder cancer, endometrial cancer and breast cancer risk [ 15 , 32 , 33 ]. All of these indicated that CACNA1C could also be a prognostic predictor for patients with OC.…”

Section: Discussionmentioning

confidence: 99%

CACNA1C is a prognostic predictor for patients with ovarian cancer

Chang

Dong

2021

J Ovarian Res

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Background CACNA1C, as a type of voltage-dependent calcium ion transmembrane channel, played regulatory roles in the development and progress of multiple tumors. This study was aimed to analyze the roles of CACNA1C in ovarian cancer (OC) of overall survival (OS) and to explore its relationships with immunity. Methods Single gene mRNA sequencing data and corresponding clinical information were obtained from The Cancer Genome Atlas Database (TCGA) and the International Cancer Genome Consortium (ICGC) datasets. Gene set enrichment analysis (GSEA) was used to identify CACNA1C-related signal pathways. Univariate and multivariate Cox regression analyses were applied to evaluate independent prognostic factors. Besides, associations between CACNA1C and immunity were also explored. Results CACNA1C had a lower expression in OC tumor tissues than in normal tissues (P < 0.001), with significant OS (P = 0.013) and a low diagnostic efficiency. We further validated the expression levels of CACNA1C in OC by means of the ICGC dataset (P = 0.01), qRT-PCR results (P < 0.001) and the HPA database. Univariate and multivariate Cox hazard regression analyses indicated that CACNA1C could be an independent risk factor of OS for OC patients (both P < 0.001). Five significant CACNA1C-related signaling pathways were identified by means of GSEA. As for genetic alteration analysis, altered CACNA1C groups were significantly associated with OS (P = 0.0169), progression-free survival (P = 0.0404), disease-free survival (P = 0.0417) and disease-specific survival (P = 9.280e-3), compared with unaltered groups in OC. Besides, CACNA1C was dramatically associated with microsatellite instability (MSI) and immunity. Conclusions Our results shed light on that CACNA1C could be a prognostic predictor of OS in OC and it was closely related to immunity.

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“…Upregulation of CCNE1 is also observed in aggressive osteosarcoma 70 and also implicated in cisplatin resistance in bladder cancer 71 . Differential expression of CCNE1 is also observed in other cancers including non‐small cell lung cancer (NSCLC), 72 bladder, 73 breast 74 and hepatocellular carcinoma 75 …”

Section: Discussionmentioning

confidence: 99%