Bladder Cancer Genetic Susceptibility. A Systematic Review

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.