PURPOSE: Bacillus Calmette-Gu  rin (BCG)-treatment is an established treatment for @entity150 , but its mechanisms of action are not fully understood. High-risk non-muscle invasive @entity150 (NMIBC)- @entity1 failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of @entity1 at risk for BCG-failure is of high priority. Several studies indicate a role for @entity842 (NO) in the cytotoxic effect that BCG exerts on @entity150 cells. In this study we investigated whether @entity3623 ( @entity3623 )-gene polymorphisms, @entity3623 -promoter microsatellite (CCTTT)n, and the @entity9554 -polymorphisms @entity16587 ( @entity16586 ) and @entity15379 ( @entity26293 ), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. MATERIALS AND METHODS: All NMIBC- @entity1 from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on @entity5 ( @entity5 ), recurrence and progression in @entity1 with varying @entity3623 -genotypes were studied using Cox proportional hazard-models and log rank tests. RESULTS: BCG-treatment resulted in significantly better survival in @entity1 without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in @entity1 with a long version ((CCTTT)n    13 repeats) of the @entity3623 -promoter microsatellite. The @entity9554 - @entity16586 (TT) and @entity26293 (GG)-genotypes showed decreased risk for @entity5 (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated @entity1 that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated @entity1 that did not benefit from BCG-treatment. CONCLUSIONS: Our results suggest that the investigated polymorphisms influence @entity1 response to BCG-treatment and thus may serve as possible markers for identification of BCG-failures.

Outcome after BCG treatment for @entity150 may be influenced by polymorphisms in the @entity3623 and XXXX genes.

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity16586 :: ('rs2070744', 'SNP') :: ['rs2070744'] @entity26293 :: ('rs1799983', 'SNP') :: ['rs1799983'] @entity9554 :: ('4846', 'Gene') :: ['NOS3'] @entity5 :: ('MESH:D009369', 'Disease') :: ['CSD', 'cancer-specific death'] @entity16587 :: ('c|SUB|T|-786|C', 'DNAMutation') :: ['-786T>C'] @entity150 :: ('MESH:D001749', 'Disease') :: ['bladder cancer', 'bladder-cancer'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity3623 :: ('4843', 'Gene') :: ['NOS2', 'NO-synthase', 'NOS'] @entity15379 :: ('p|SUB|E|298|D', 'ProteinMutation') :: ['Glu298Asp']
@entity9554 :: (4846,Gene) :: ['NOS3']
