Urinary Bladder Cancer Susceptibility Markers. What Do We Know about Functional Mechanisms?

Abstract

Genome-wide association studies (GWAS) have been successful in the identification of the several urinary bladder cancer (UBC) susceptibility loci, pointing towards novel genes involved in tumor development. Despite that, functional characterization of the identified variants remains challenging, as they mostly map to poorly understood, non-coding regions. Recently, two of the UBC risk variants (PSCA and UGT1A) were confirmed to have functional consequences. They were shown to modify bladder cancer risk by influencing gene expression in an allele-specific manner. Although the role of the other UBC risk variants is unknown, it can be hypothesized—based on studies from different cancer types—that they influence cancer susceptibility by alterations in regulatory networks. The insight into UBC heritability gained through GWAS and further functional studies can impact on cancer prevention and screening, as well as on the development of new biomarkers and future personalized therapies.

Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors

“…But genetic variation matters the most (Dudek et al, 2013). Nowadays, genome-wide association studies (GWAS) which based on the casecontrol design can predict underlying cancers (Dudek et al, 2013).…”

“…But genetic variation matters the most (Dudek et al, 2013). Nowadays, genome-wide association studies (GWAS) which based on the casecontrol design can predict underlying cancers (Dudek et al, 2013). And as the epidermal growth factor receptor (EGFR) is frequently over-expressed in bladder cancer (Kompier et al, 2010), it can be an important therapeutic target.…”

Increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of bladder cancer

“…A wide range of environmental risk factors has been identified among which are tobacco smoking, consumption of arsenic-contaminated water, occupational exposure to aromatic amines and polycyclic hydrocarbons, and chronic infection with Schistosoma species (Matullo et al , 2015). Several germline variants have also been recognised as contributors to BC risk (Dudek et al , 2013). …”

Genetic Variation in PSCA is Associated with Bladder Cancer Susceptibility in a Korean Population

“…However, candidate gene studies lacked sufficient power to identify 1 the genetic loci for clarification of the mechanisms of bladder cancer (Dudek et al, 2013). Recently, genomewide association studies (GWAS) have permitted the identification of novel susceptibility loci in the human genome associated with many complex diseases, including cancer (Dudek et al, 2013).…”

“…However, candidate gene studies lacked sufficient power to identify 1 the genetic loci for clarification of the mechanisms of bladder cancer (Dudek et al, 2013). Recently, genomewide association studies (GWAS) have permitted the identification of novel susceptibility loci in the human genome associated with many complex diseases, including cancer (Dudek et al, 2013). To date, three GWAS for bladder cancer risk have been conducted, and eight single nucleotide polymorphisms (SNPs) were identified near the following genes: MYC (8q24), TP63 (3q28), PSCA (8q24), FGFR3/TACC3 (4p16), CBX6/ APOBEC3A (22q13), CCNE1 (19q12), UGT1A (2q37), and SLC14A1 (18q12) (Kiemeney et al, 2008;Wu et al, 2009;Kiemeney et al, 2010;Rothman et al, 2010;Rafnar et al, 2011).…”