title: Glutathione S-Transferase Gene Polymorphisms and Treatment Outcome in Cervical Cancer Patients under Concomitant Chemoradiation.
abstract: OBJECTIVE
  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.
authors.affiliation: Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow -226007, Uttar Pradesh, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abbas
authors.affiliation: Department of Radiotherapy, King George's Medical University, Lucknow-226003, Uttar Pradesh, India.
authors.forename: Vandana Singh
authors.initials: VS
authors.lastname: Kushwaha
authors.affiliation: Department of Radiotherapy, King George's Medical University, Lucknow-226003, Uttar Pradesh, India.
authors.forename: Kirti
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow -226007, Uttar Pradesh, India.
authors.forename: Monisha
authors.initials: M
authors.lastname: Banerjee
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000379:methods; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D010100:Oxygen; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human