Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.
Redox Biol
; 6: 272-277, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-26298202
ABSTRACT
PURPOSE:
Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. MATERIALS ANDMETHODS:
All NMIBC-patients 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 cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests.RESULTS:
BCG-treatment resulted in significantly better survival in patients without (Log rank p=0.006; HR 0.12, p=0.048), but not in patients with a long version ((CCTTT)n â§13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (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 patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment.CONCLUSIONS:
Our results suggest that the investigated polymorphisms influence patient response to BCG-treatment and thus may serve as possible markers for identification of BCG-failures.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
/
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
3_tuberculosis
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4_tuberculosis
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6_bladder_cancer
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6_other_malignant_neoplasms
Asunto principal:
Neoplasias de la Vejiga Urinaria
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Carcinoma in Situ
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Carcinoma de Células Transicionales
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Óxido Nítrico Sintasa de Tipo II
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Óxido Nítrico Sintasa de Tipo III
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Mycobacterium bovis
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Recurrencia Local de Neoplasia
/
Antineoplásicos
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Redox Biol
Año:
2015
Tipo del documento:
Article