title: Predictive Value of NRAMP1 and HGPX1 Gene Polymorphism for Maintenance BCG Response in Non-muscle-invasive Bladder Cancer.
abstract: OBJECTIVE
  To assess the potential predictive value of natural resistance-associated macrophage protein 1 (NRAMP1) and human glutathione peroxidase 1 (hGPX1) polymorphism in non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation, we conducted an original ancillary multicenter study.
  
  
  METHODS
  We evaluated patients included in the multicenter URO-BCG 4 trial, who received three weekly instillations of one-third dose BCG every 6 months (group I) or two weekly instillations every 3 months (group II) for 3 years. For clinical evaluation we also evaluated tumor recurrence and muscle progression. NRAMP1 and hGPX1 polymorphism analyses were performed on blood DNA. NRAMP1 exon 15 and hGPX1 exon 1c were amplified using Type-it Microsatellite PCR Kit® for multiplex polymerase chain reaction.
  
  
  RESULTS
  From June 2004 to April 2010, 146 randomized patients were included in this retrospective study. Blood samples were obtained from 107 patients. With 36 months of follow-up, 13.6% of patients had a tumor recurrence and muscle-invasive progression was observed in 4.3% of patients. Concerning NRAMP1 D543N polymorphism, patients with allele A had no tumor recurrence or muscle-invasive progression. No significant difference was observed in gene polymorphism distribution between groups I and II. Moreover, we did not observe any significant association of gene polymorphisms, tumor recurrence or muscle-invasive progression, event time and disease-free survival.
  
  
  CONCLUSIONS
  Our results suggest that no significant difference was found for NRAMP1 and hGPX1 gene polymorphisms associated with recurrence time, muscle invasion frequency and disease-free survival, nevertheless, we observed that the NRAMP1 D543N GG genotype group had a shorter time to tumor recurrence.
authors.affiliation: Department of Urology, Rouen University Hospital, Rouen, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lenormand
authors.affiliation: BioTechnology Laboratory, Science and Technology University, Le Havre, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couteau
authors.affiliation: Department of Urology, Rouen University Hospital, Rouen, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Nouhaud
authors.affiliation: BioTechnology Laboratory, Science and Technology University, Le Havre, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Maillet
authors.affiliation: Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bou
authors.affiliation: Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gobet
authors.affiliation: Department of Urology, Rouen University Hospital, Rouen, France Clinical Investigation Center, Inserm 6204, Onco-Urology Group, Rouen, France christian.pfister@chu-rouen.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Pfister
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D027682:Cation Transport Proteins / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000382:microbiology / Q000473:pathology*; D009163:Mycobacterium bovis / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D000094765:Glutathione Peroxidase GPX1; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; D000099173:Natural Resistance-associated Macrophage Protein 1
keywords: BGG; NRAMP1; bladder cancer; hGPX1; polymorphism; recurrence