Bladder cancer course, four genetic high-risk variants, and histopathological findings

Thura Kadhum; Silvia Selinski; Meinolf Blaszkewicz; Jörg Reinders; Emanuel Roth; Frank Volkert; Daniel Ovsiannikov; Oliver Moormann; Holger Gerullis; Dimitri Barski; Thomas Otto; Svetlana Höhne; Jan G Hengstler; Klaus Golka

doi:10.17179/excli2023-5862

Bladder cancer course, four genetic high-risk variants, and histopathological findings

EXCLI J. 2023 Aug 18:22:867-879. doi: 10.17179/excli2023-5862. eCollection 2023.

Authors

Affiliations

¹ Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.
² Specialist Clinic for Psychosomatic Rehabilitation, Mittelrhein-Klinik, Boppard - Bad Salzig, Germany.
³ Department of Urology, Evangelic Hospital, Paul-Gerhardt Foundation, Lutherstadt Wittenberg, Germany.
⁴ St.-Josefs-Hospital Dortmund-Hoerde, Dortmund, Germany.
⁵ Rheinland Klinikum Lukaskrankenhaus Neuss, Neuss, Germany.

Abstract

Urinary bladder cancer, a smoking and occupation related disease, was subject of several genome-wide association studies (GWAS). However, studies on the course of the disease based on GWAS findings differentiating between muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC) are rare. Thus we investigated 4 single nucleotide polymorphisms (SNPs) detected in GWAS, related to the genes coding for TACC3 (transforming, acidic coiled-coil containing protein 3), for FGFR3 (fibroblast growth factor receptor 3), for PSCA (prostate stem cell antigen) and the genes coding for CBX6 (chromobox homolog 6) and APOBEC3A (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A). This study is based on 712 bladder cancer patients and 875 controls from 3 different case control studies in Germany. The 4 SNPs of interest (PSCA rs2294008 and rs2978974, FGFR3-TACC3 rs798766, and CBX6-APOBEC3A rs1014971) were determined by real-time polymerase chain reaction. The distribution of the 4 SNPs does not vary significantly between cases and controls in the entire study group and in the 3 local subgroups, including two former highly industrialized areas and a region without such history. Also, no significant differences in the bladder cancer subgroups of MIBC and NMIBC were observed. The 4 investigated SNPs do not noticeably contribute differently to the bladder cancer risk for the bladder cancer subgroups of MIBC and NMIBC.

Keywords: CBX6-APOBEC3A gene region rs1014971; FGFR3-TACC3 gene region rs798766; PSCA gene rs2294008 and rs2978974; muscle invasive bladder cancer (MIBC); non-muscle invasive bladder cancer (NMIBC).