Back to Search
Start Over
Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.
- Source :
-
Redox biology [Redox Biol] 2015 Dec; Vol. 6, pp. 272-277. Date of Electronic Publication: 2015 Aug 10. - Publication Year :
- 2015
-
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.<br />Materials and Methods: 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.<br />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 ≧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.<br />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.<br /> (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Aged
Alleles
Carcinoma in Situ diagnosis
Carcinoma in Situ genetics
Carcinoma in Situ mortality
Carcinoma, Transitional Cell diagnosis
Carcinoma, Transitional Cell genetics
Carcinoma, Transitional Cell mortality
Female
Gene Expression
Humans
Male
Middle Aged
Neoplasm Recurrence, Local diagnosis
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local mortality
Neoplasm Staging
Polymorphism, Genetic
Prognosis
Promoter Regions, Genetic
Proportional Hazards Models
Prospective Studies
Treatment Outcome
Urinary Bladder Neoplasms diagnosis
Urinary Bladder Neoplasms genetics
Urinary Bladder Neoplasms mortality
Antineoplastic Agents therapeutic use
Carcinoma in Situ therapy
Carcinoma, Transitional Cell therapy
Mycobacterium bovis chemistry
Neoplasm Recurrence, Local therapy
Nitric Oxide Synthase Type II genetics
Nitric Oxide Synthase Type III genetics
Urinary Bladder Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2213-2317
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Redox biology
- Publication Type :
- Academic Journal
- Accession number :
- 26298202
- Full Text :
- https://doi.org/10.1016/j.redox.2015.08.008