title: NRAMP1 and hGPX1 gene polymorphism and response to bacillus Calmette-Guérin therapy for bladder cancer.
abstract: BACKGROUND
  The natural resistance-associated macrophage protein 1 (NRAMP1) gene is associated with susceptibility to Mycobacterium tuberculosis in humans and to bacillus Calmette-Guérin (BCG) in mice. The detoxification enzyme, human glutathione peroxidase 1 (hGPX1), is associated with recurrence of bladder cancer (BCa).
  
  
  OBJECTIVE
  To determine whether NRAMP1 and hGPX1 gene polymorphisms correlate with response to BCG immunotherapy for non-muscle-invasive BCa (NMIBC).
  
  
  METHODS
  DNA was obtained from the peripheral blood of 99 NMIBC patients who were prospectively randomized to receive postresection intravesical BCG (81 mg [n=50] or 27 mg [n=19]) or BCG (27 mg) with interferon alpha (IFN-α; n=30). The median follow-up time was 60 mo.
  
  
  METHODS
  Intravesical BCG or BCG-IFN-α.
  
  
  METHODS
  Restriction fragment length polymorphism (RFLP) analysis was performed to identify polymorphisms in the NRAMP1 promoter region (GT repeat number) and at position 543 (aspartate [D] and/or asparagine [N] expression) within the NRAMP1 protein (D543N) and position 198 (proline and/or leucine expression) within the hGPX1 protein (Pro198Leu). Data were analyzed using χ(2) analysis, multivariate analysis, and Kaplan-Meier curves.
  
  
  CONCLUSIONS
  On univariate analysis, the NRAMP1 D543N G:G genotype had decreased cancer-specific survival (CSS; p=0.036). The hGPX1 CT genotype (Pro-Leu) had decreased recurrence time (p=0.03) after BCG therapy. On multivariate analysis, patients with the NRAMP1 D543N G:G genotype and allele 3 (GT)n polymorphism had decreased recurrence time (p=0.014 and p=0.03) after BCG therapy. The limitation of this study was its small sample size.
  
  
  CONCLUSIONS
  Polymorphisms of the NRAMP1 and hGPX1 genes may be associated with recurrence of BCa after BCG immunotherapy.
authors.affiliation: Department of Urology, National University Health System, Singapore. surce@nus.edu.sg
authors.forename: Edmund
authors.initials: E
authors.lastname: Chiong
authors.forename: Arshvin
authors.initials: A
authors.lastname: Kesavan
authors.forename: Ratha
authors.initials: R
authors.lastname: Mahendran
authors.forename: Yiong Huak
authors.initials: YH
authors.lastname: Chan
authors.forename: Jen Hwei
authors.initials: JH
authors.lastname: Sng
authors.forename: Yew Koon
authors.initials: YK
authors.lastname: Lim
authors.forename: Revathi
authors.initials: R
authors.lastname: Kamaraj
authors.forename: Theresa M C
authors.initials: TM
authors.lastname: Tan
authors.forename: Kesavan
authors.initials: K
authors.lastname: Esuvaranathan
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000094765:Glutathione Peroxidase GPX1; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D027682:Cation Transport Proteins; D005979:Glutathione Peroxidase; D007155:Immunologic Factors; D016898:Interferon-alpha; D000094765:Glutathione Peroxidase GPX1; D000099173:Natural Resistance-associated Macrophage Protein 1; C000722067:GPX1 protein, human