title: The predictive value of GSTT1 polymorphisms in predicting the early response to induction BCG therapy in patients with non-muscle invasive bladder cancer.
abstract: BACKGROUND
  We evaluated the predictive value of glutathione S transferase mu (GSTM1) and theta (GSTT1) polymorphisms in early response to bacillus Calmette-Guérin (BCG) induction therapy in patients with primary non-muscle invasive bladder cancer.
  
  
  METHODS
  GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction using blood genomic DNA from 135 patients with primary non-muscle invasive bladder cancer who were being treated with a single induction course of BCG. BCG nonresponsiveness (early BCG failure) was defined as a tumor recurrence or progression within 12 months after BCG induction therapy. The predictive value of GST polymorphisms was evaluated by Kaplan-Meier analysis and multivariate logistic regression models.
  
  
  RESULTS
  Patients carrying a GSTT1-positive genotype demonstrated a higher likelihood of early BCG failure regardless of cigarette smoking. After stratification based on the tumor stage and grade, the high-risk group (T1G3) with a GSTT1-positive genotype showed a 14-fold higher risk of early BCG failure compared with those with a GSTT1-null genotype. In a combined analysis of 2 genes, the GSTT1-positive/GSTM1-null genotype had a higher risk of BCG nonresponsiveness compared with the GSTT1-null/GSTM1-null genotype (odds ratio = 4.17, 95% CI: 1.54-11.26). By multivariate logistic regression analysis, the GSTT1-positive genotype was an independent predictor of early BCG failure (odds ratio = 3.67, 95% CI: 1.61-8.38). Kaplan-Meier estimates revealed a significant difference in disease-free survival depending on the GSTT1 genotype (log rank test, P = 0.038).
  
  
  CONCLUSIONS
  The results of this study suggest that the GSTT1-positive genotype is an independent predictor of early BCG failure. These results can help determine whether patients would benefit from adjuvant BCG treatment or may require more aggressive alternative therapies.
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Kang
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Dong-Un
authors.initials: DU
authors.lastname: Tchey
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Chunri
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Yong-June
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Section of Urologic Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ.
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea. Electronic address: wjkim@chungbuk.ac.kr.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy
chemical_list: D001500:BCG Vaccine; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1
keywords: BCG immunotherapy; Non–muscle invasive bladder cancer; Polymorphism; Prognosis