Genetic polymorphisms, methylation, and expression levels in the GSTP1 and MGMT genes in urothelial bladder tumors

Alteration in DNA repair and metabolism genes can affect the maintenance of DNA integrity or xenobiotics metabolism, potentially leading to DNA damage accumulation. The present study investigated the association between polymorphisms in Glutathione S-Transferase Pi 1 (GSTP1, rs1695) and O-6-Methylguanine-DNA Methyltransferase (MGMT, rs2308321) genes with urothelial bladder cancer (UBC) susceptibility and prognosis. Furthermore, the methylation patterns of the promoter region of these genes were analyzed in tumor and non-tumor bladder tissues, besides MGMT gene expression in tumor samples.

Blood samples of 295 patients and 295 healthy controls were genotyped using TaqMan probe assays. The DNA of 39 bladder tumors and 4 adjacent non-tumor samples were used in the Methylation-Sensitive High-Resolution Melting (MS-HRM) assay. Neither polymorphism conferred UBC susceptibility/protection or affected tumor grade, muscle invasion, and recurrence). GSTP1 did not show methylation in the promoter region, while in the MGMT gene, all samples presented heterogeneous methylation with no significant differences between tumor and non-tumor tissues. High MGMT expression was associated with low-grade (p = 0.0153) and trends related to non-invasive tumors (p = 0.070).

In our cohort, MGMT expression seems helpful as a biomarker of good prognosis (low-grade and absence of muscle invasion). A heterogeneous methylation pattern in the MGMT gene requires additional investigation to elucidate its potential implications.