Interplay of host genome and tumour genome in bladder cancer

Abstract

Aim. To determine the influence of the polymorphic variants of the base (OGG1 and XRCC1) and nucleotide (ERRC2/XPD and ERRC6/CSB) excision repair genes on the mutational and epigenetic status of bladder tumors. Methods. For this study, we used previously obtained data on the polymorphism of DNA repair genes in bladder cancer (BC) patients, whose tumor tissue samples were analyzed for the presence of key mutational and epigenetic changes. Results. Genotypes containing at least one minor OGG1 rs1052133 allele were significantly associated with an increased frequency of RAS family gene mutations and a reduced frequency of PIK3CA mutations. The polymorphisms of both base excision repair genes influenced the epigenetic variability of urothelial carcinomas, the modifying effect of OGG1 rs1052133 manifesting in ISL1 methylation and XRCC1 rs25487 impacting p16 or TIMP3 methylation. The minor ERRC6/CSB rs2228526 allele was associated with RAS mutations and lack of TIMP3 methylation. Likewise, carriers of the genotypes containing at least one minor ERRC2/XPD rs1799793 allele were less frequently found to have methylated RUNX3 gene in tumor tissues. Conclusions. The polymorphisms of the base (OGG1, XRCC1) and nucleotide (ERRC2/XPD, ERRC6/CSB) excision repair genes modify the mutational and epigenetic variability of a number of key BC genes. The study of the mechanisms of such interactions is necessary for understanding the molecular basis of BC pathogenesis.
 Keywords: bladder cancer, OGG1, XRCC1, ERRC2/XPD, ERRC6/CSB gene polymorphism, mutation, methylation.