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Rev Mex Urol. 2017 July;77(4):301-303. DOI: https://doi.org/10.24245/revmexurol.v77i4.1477
Meng XY,1 Shi MJ2
1 Centro para la Medicina Basada en Evidencia y la Medicina Translacional, Hospital Zhongnan de la Universidad de Wuhan, China.
2 Institut Curie, PSL Research University, CNRS, UMR 144, Paris, France.
Bladder cancer is a common malignant tumor and genetic factors can play an important role in its development, recurrence, and progression. The association between the risk for bladder cancer and the glutathione S-transferase (GST) T1 and M1 gene polymorphisms has been the subject of debate in recent meta-analyses.1 However, there is currently no complete review of their prognostic importance and inconsistencies have been observed in the primary studies. We therefore carried out a review of the literature on this theme to summarize the available information.
A thorough bibliographic search of the PubMed database was performed. Nine relevant articles were selected that were published between 2005 and 2015, evaluating patients with bladder cancer, the association between the GSTT1 and GSTM1 polymorphisms (null vs positive), and outcome.2-10 Three of the studies included patients with superficial bladder cancer (SBC) and invasive bladder cancer (IBC),2-3,6 four focused only on SBC,4-5,9-10 and two of the studies were on IBC.7-8Five of the studies were conducted on Korean populations 4-5,8-9 and four were conducted on white patients.3,6-7,10 The first study, carried out on 153 patients with bladder cancer, showed no significant prognostic impact of the GSTT1 polymorphism, but the GSTM1-positive genotype significantly increased the risk for disease progression more than 3-fold (p=0.016).2 The first relevant study on Caucasian patients was published in 2010. Those authors reported a 1.9-fold greater risk for death in GSTM1-negative patients (p=0.05).3 The research group of Ha et al. examined only patients with SBC. They found that the GSTT1-positive genotype led to a 1.6-fold greater risk for recurrence (p=0.043) and a 3.4-fold greater risk for progression (p=0.006), and that the GSTM1-negative genotype was associated with a 2.7-fold greater risk for recurrence (p=0.031).4-5 In a 2012 study on 213 German patients with bladder cancer, Roth et al. found that GSTT1 positivity reduced the risk for recurrence by 40% (p=0.007) and that GSTM1 did not significantly influence that variable (p=0.36).6 In the 2013 study by Djukic et al., they reported their findings on a group of Serbian patients with invasive bladder cancer. According to their results, the GSTT1-positive genotype was a risk factor for poor overall survival (p=0.028), but the impact of the GSTM1 polymorphism was not significant (p=0.694).7 The Korean research team of Kang et al. separately examined the prognostic performance of the GSTT1 and GSTM1 gene polymorphisms in patients with superficial bladder cancer and invasive bladder cancer. In the patients with invasive bladder cancer, the GSTT1-null genotype significantly increased the risk for disease progression and cancer-specific survival by approximately 3-fold (p=0.001 and 0.003, respectively), but found no significant effect for the GSTM1 polymorphism. In the patients with superficial bladder cancer, GSTT1 positivity was correlated with a greater risk for recurrence (p=0.038).8-9 Lacombe et al. conducted the most recent study, reporting a nonsignificant difference in cancer recurrence between the GSTM1-null and GSTM1-positive genotypes in a group of Canadian patients with superficial bladder cancer.10 Figure 1 illustrates the information described above.
In short, there is not much information available on this theme and we found great inconsistencies between the results of the different studies. The precise prognostic importance of the GSTM1 and GSTT1 polymorphisms has not been determined in relation to bladder cancer. The difference in type of disease (superficial or invasive) and ethnic origin (Asian, Caucasian) can explain that heterogeneity. Nevertheless, given the insufficient amount of information available, no conclusions can be reached. Further studies and verifications are needed that have adequate sample sizes, rigorous design, thorough analysis, and standard reporting of the results.
No financial support was received in relation to this letter.
Conflict of interest
The authors declare that there is no conflict of interest.
3. Norskov MS, Frikke-Schmidt R, Bojesen SE, et al. Copy number variation in glutathione-S-transferase T1 and M1 predicts incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer in the general population. Pharmacogenomics J. 2011;11(4):292-9.
7. Djukic TI, Savic-Radojevic AR, Pekmezovic TD, et al. Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients. PloS One. 2013;8(9):e74724.
9. Kang HW, Tchey DU, Yan C, et al. The predictive value of GSTT1 polymorphisms in predicting the early response to induction BCG therapy in patients with non-muscle invasive bladder cancer. Urol Oncol. 2014;32(4):458-65.
10. Lacombe L, Fradet V, Levesque E, et al. Phase II Drug-Metabolizing Polymorphisms and Smoking Predict Recurrence of Non-Muscle-Invasive Bladder Cancer: A Gene-Smoking Interaction. Cancer Prev Res (Phila). 2016;9(2):189-95.