# Influence of Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and N-acetyltransferase 2 (NAT2) Variants on Bladder Cancer Progression and Recurrence Rating: A Bosnian and Herzegovinian Case-Control Study

**Authors:** Osman Hadziosmanovic, Benjamin Kulovac, Amina Valjevac, Almir Fajkić, Izabela Uzar, Grazyna Adler

PMC · DOI: 10.7759/cureus.91948 · 2025-09-09

## TL;DR

This study found that a specific genetic variant, GSTT1 T--, is linked to higher bladder cancer recurrence and progression in Bosnian and Herzegovinian patients.

## Contribution

The study identifies GSTT1 T-- as an independent predictor of bladder cancer recurrence and progression in a specific population.

## Key findings

- The GSTT1 T-- genotype was associated with higher one- and five-year probabilities of bladder cancer progression.
- GSTT1 T-- genotype was an independent predictor of both recurrence and progression in bladder cancer patients.
- Age and GSTT1 T-- genotype were independent predictors for five-year recurrence and progression probabilities.

## Abstract

Introduction: It is suggested that bladder cancer (BC) development is linked to glutathione S-transferase (GST) enzymes. This study aimed to determine the correlation between glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase Theta 1 (GSTT1), and N-acetyltransferase 2 (NAT2) variants with BC progression and recurrence rating.

Materials and methods: This study included 105 Bosnian and Herzegovinian subjects: 60 patients with histopathologically confirmed BC and 45 controls without urological diseases. GSTM1, GSTT1 (rs36631 and rs17856199, respectively), and NAT2 (rs1799929, rs1799930, and rs1799931) were investigated.

Results: Both one- and five-year probabilities of progression were not significantly different in GSTM1 and NAT2 polymorphisms. One-year probability of progression was significantly higher in the GSTT1 T-- (null) than the T++ (wildtype) genotype (14.7% (±6.9) vs. 8.9% (±6.7), respectively; p=0.048). Five-year probability of progression was significantly higher in the GSTT1 T-- than the T++ genotype (39.4% (±14.7) vs. 25.5% (±16.6), respectively; p=0.045). THE GSTT1 T-- genotype was an independent predictor in the one-year probability of recurrence and progression (p=0.03 and p=0.01, respectively). GSTT1 T-- genotype and age were independent predictors for the five-year probability of recurrence (p=0.032 and p=0.04, respectively) as well as independent predictors of the five-year probability of progression (p=0.012 and p=0.03, respectively).

Conclusions: The GSTT1 T-- genotype was an independent predictor in the one- and five-year probabilities of both recurrence and progression of BC. GSTT1 rs17856199 may be a significant factor in the development of tumors and the course of disease in Bosnian and Herzegovinian BC patients.

## Linked entities

- **Genes:** GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944], GSTT1 (glutathione S-transferase theta 1) [NCBI Gene 2952], NAT2 (N-acetyltransferase 2) [NCBI Gene 10]
- **Proteins:** GSTT1 (glutathione S-transferase THETA 1)
- **Diseases:** bladder cancer (MONDO:0004986)

## Full-text entities

- **Genes:** NAT2 (N-acetyltransferase 2) [NCBI Gene 10] {aka AAC2, NAT-2, PNAT}, GSTK1 (glutathione S-transferase kappa 1) [NCBI Gene 373156] {aka GST, GST 13-13, GST13, GST13-13, GSTK1-1, hGSTK1}, GSTT1 (glutathione S-transferase theta 1) [NCBI Gene 2952], GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944] {aka GST1, GSTM1-1, GSTM1a-1a, GSTM1b-1b, GTH4, GTM1}
- **Diseases:** tumors (MESH:D009369), BC (MESH:D001749), urological diseases (MESH:D014570)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs1799931, rs1799929, rs1799930, rs36631, rs17856199

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Source: https://tomesphere.com/paper/PMC12515255