Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Nov 16;10(11):e0142501.
doi: 10.1371/journal.pone.0142501. eCollection 2015.

Glutathione S-Transferase Gene Polymorphisms and Treatment Outcome in Cervical Cancer Patients under Concomitant Chemoradiation

Mohammad Abbas  1 , Vandana Singh Kushwaha  2 , Kirti Srivastava  2 , Monisha Banerjee  1
Affiliations

Glutathione S-Transferase Gene Polymorphisms and Treatment Outcome in Cervical Cancer Patients under Concomitant Chemoradiation

Mohammad Abbas et al. PLoS One. .

Abstract

Purpose: Cisplatin based concomitant chemoradiation (CRT) is the standard treatment for locally advanced cervical cancer (CC). Glutathione S-transferase (GST), a phase II antioxidant enzyme is induced by oxidative stress generated by drugs and reactive oxidants. The present study was undertaken to evaluate the association of GSTM1, T1 and P1 polymorphisms with the outcome of CRT treatment in CC patients.

Methods: A total of 227 cervical cancer patients with stages IIB-IIIB treated with the same chemoradiotherapy regimen were enrolled and genotyped for GSTM1, T1 and P1 gene polymorphisms by multiplex polymerase chain reaction (mPCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Overall survival was evaluated using Kaplan-Meier survival function and Cox proportional hazards model. All data were analyzed using SPSS (version 21.0).

Results: Stratified analysis showed that GSTM1 null (M1-) genotype was associated with a significantly better survival among patients with stage IIB cervical cancer (log-rank P = 0.004) than cases with stage IIIA/IIIB. Death and recurrence were significantly higher in patients with GSTM1 present genotype (M1+) (P = 0.037 and P = 0.003 respectively) and those with M1- showed reduced hazard of death with an adjusted hazard ratio 'HR' of 0.47 (95% CI, 0.269-0.802, P = 0.006). Women with M1- genotype as well as in combination with GSTT1 null (T1-), GSTP1 (AG+GG) and GSTT1 null/GSTP1 (AG+GG) showed better survival and also reduced risk of death (HR = 0.31, P = 0.016; HR = 0.45, P = 0.013; HR = 0.31, P = 0.02 respectively).

Conclusions: To the best of our knowledge, this is the first study to correlate the association of GSTM1, T1 and P1 gene polymorphisms with treatment outcome of CRT treated CC patients. Our results suggested that individuals with GSTM1 null genotype and in combination with GSTT1 null and GSTP1 (AG+GG) had a survival advantage. Such genetic studies may provide prognostic information in CRT treated CC patients.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Kaplan-Meier function for overall survival among women treated for cervical cancer, by GSTM1, T1 and P1 genotypes.
Survival difference by log-rank test.
Fig 2
Fig 2. Kaplan-Meier function for overall survival among women treated for cervical cancer, by GSTM1, T1 and P1 genotypes in combination.
Survival difference by log-rank test.
See this image and copyright information in PMC

References

    1. Vale C, Tierney JF, Stewart LA, Brady M, Dinshaw K, Jakobsen A, et al. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematics review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 2008;26:5802–5812. 10.1200/JCO.2008.16.4368 - DOI - PMC - PubMed
    1. Nogueira A, Catarino R, Faustino I, Nogueira-Silva C, Figueiredo T, Lombo L, et al. Role of the RAD51 G172T polymorphism in the clinical outcome of cervical cancer patients under concomitant chemoradiotherapy. Gene 2012;504:279–283. 10.1016/j.gene.2012.05.037 - DOI - PubMed
    1. Ekhart C, Rodenhuis S, Smits PH, Beijnen JH, Huitema AD. An overview of the relations between polymorphisms in drug metabolising enzymes and drug transporters and survival after cancer drug treatment. Cancer Treat Rev 2009;35:18–31. 10.1016/j.ctrv.2008.07.003 - DOI - PubMed
    1. Lando M, Holden M, Bergersen LC, Svendsrud DH, Stokke T, Sundfør K,et al. Gene dosage, expression, and ontology analysis identifies driver genes in the carcinogenesis and chemoradioresistance of cervical cancer. PLoS Genetics 2009;5:e1000719 10.1371/journal.pgen.1000719 - DOI - PMC - PubMed
    1. Goekkurt E, Hoehn S, Wolschke C, Wittmer C, Stueber C, Hossfeld DK, et al. Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS)—novel predictors for response and survival in gastric cancer patients. Br J Cancer 2006;94:281–286. - PMC - PubMed

Publication types

MeSH terms