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Basic Research

Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy

Prostate Cancer and Prostatic Diseases volume 16, pages 28–34 (2013)Cite this article

Subjects

Abstract

Background:

Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence.

Methods:

We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A>G (p.105 Ile>Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan–Meier curves and Cox proportional hazard models were used to evaluate these associations.

Results:

Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P=0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR)=3.16, 95% confidence interval (95% CI)=1.41–7.06, P=0.005) and multivariate models (HR=3.01, 95% CI=1.13–8.02, P=0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P=0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR=3.06, 95% CI=1.20–7.80, P=0.019).

Conclusions:

Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.

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Acknowledgements

We acknowledge Diego Fernandez-Ortiz for his help with the clinical records. This work was financially supported by Agencia Nacional de Promoción Científica y Tecnológica: PICT 2006-0228 and PICT-RAICES 2006-0367. National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institute of Health (NIH), through Grant Award Number TL1RR031992.

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Author notes

  1. D B Leonardi and A Shahabi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Chemistry, School of Sciences, University of Buenos Aires—IQUIBICEN, CONICET, Buenos Aires, Argentina

    J Cotignola, D B Leonardi, A D Acuña, A De Siervi & E Vazquez

  2. Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, Los Angeles, CA, USA

    A Shahabi & M C Stern

  3. Department of Genitourinary Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    N Navone

  4. Urology Service, Hospital de Clínicas ‘José de San Martín’, University of Buenos Aires, Buenos Aires, Argentina

    C Scorticati & O Mazza

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  1. J Cotignola
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Correspondence to J Cotignola.

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Cotignola, J., Leonardi, D., Shahabi, A. et al. Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy. Prostate Cancer Prostatic Dis 16, 28–34 (2013). https://doi.org/10.1038/pcan.2012.45

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