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Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

Ryk C, Koskela LR, Thiel T, Wiklund NP, Steineck G, Schumacher MC, de Verdier PJ - Redox Biol (2015)

Bottom Line: 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.Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment.

View Article: PubMed Central - PubMed

Affiliation: Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Urology, Karolinska University Hospital, 171 76 Stockholm, Sweden. Electronic address: charlotta.ryk@ki.se.

No MeSH data available.


Related in: MedlinePlus

Difference in survival after BCG-treatment. Comparison within the group of the BCG-treated patients (n=51), between those with at least one of the NOS2(CCTTT)non-L-carrier, NOS3-rs2070744(TT) or rs1799983(GG) considered to yield basal levels of NO (i.e. neither increased NOS2 gene activity, nor decreased NOS3 gene activity) (n=36/51; 70.6%; Basal level NO), and those with the NOS2(CCTTT)L-carrier, NOS3- rs2070744(CT/CC) and rs1799983(GT/TT) genotypes, who in theory have increased NOS2 gene activity and decreased activity in the NOS3 gene (n=15/51; 29.4%; High/low NO). Patients still at risk are shown for each time point in the diagrams. (A) BCG-treated patients with basal level of NOS-gene activity showed a significantly better cancer specific survival (Log-rank test: p=0.037), than BCG-treated patients with increased NOS2 and decreased NOS3-gene activity. (B) The difference in risk of disease progression between the two groups of BCG-treated patients with and without basal level of NOS-gene activity was non-significant (Log-rank test: p=0.196). (C) BCG-treated patients with basal level of NOS-gene activity had a significantly lower risk of recurrence (Log-rank test: p=0.035), than BCG-treated patients with increased NOS2 and decreased NOS3-gene activity.
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f0005: Difference in survival after BCG-treatment. Comparison within the group of the BCG-treated patients (n=51), between those with at least one of the NOS2(CCTTT)non-L-carrier, NOS3-rs2070744(TT) or rs1799983(GG) considered to yield basal levels of NO (i.e. neither increased NOS2 gene activity, nor decreased NOS3 gene activity) (n=36/51; 70.6%; Basal level NO), and those with the NOS2(CCTTT)L-carrier, NOS3- rs2070744(CT/CC) and rs1799983(GT/TT) genotypes, who in theory have increased NOS2 gene activity and decreased activity in the NOS3 gene (n=15/51; 29.4%; High/low NO). Patients still at risk are shown for each time point in the diagrams. (A) BCG-treated patients with basal level of NOS-gene activity showed a significantly better cancer specific survival (Log-rank test: p=0.037), than BCG-treated patients with increased NOS2 and decreased NOS3-gene activity. (B) The difference in risk of disease progression between the two groups of BCG-treated patients with and without basal level of NOS-gene activity was non-significant (Log-rank test: p=0.196). (C) BCG-treated patients with basal level of NOS-gene activity had a significantly lower risk of recurrence (Log-rank test: p=0.035), than BCG-treated patients with increased NOS2 and decreased NOS3-gene activity.

Mentions: Analyses of genotypes only within the group of BCG-treated patients (n=51) show that those (n=36; 70.6%) with at least one of either (1) NOS2 (CCTTT)non-L-carrier (homozygous), (2) NOS3- rs2070744 (TT) or (3) rs1799983 (GG) genotypes had a significantly better cancer specific survival (HR: 0.20; CI: 0.05–0.85; p=0.029; Log-rank test: p=0.037), and a decreased risk of recurrence (HR: 0.54; CI: 0.23–1.27; p=0.160; Log-rank test: p=0.035), than patients without these three genotypes (Fig. 1).


Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

Ryk C, Koskela LR, Thiel T, Wiklund NP, Steineck G, Schumacher MC, de Verdier PJ - Redox Biol (2015)

Difference in survival after BCG-treatment. Comparison within the group of the BCG-treated patients (n=51), between those with at least one of the NOS2(CCTTT)non-L-carrier, NOS3-rs2070744(TT) or rs1799983(GG) considered to yield basal levels of NO (i.e. neither increased NOS2 gene activity, nor decreased NOS3 gene activity) (n=36/51; 70.6%; Basal level NO), and those with the NOS2(CCTTT)L-carrier, NOS3- rs2070744(CT/CC) and rs1799983(GT/TT) genotypes, who in theory have increased NOS2 gene activity and decreased activity in the NOS3 gene (n=15/51; 29.4%; High/low NO). Patients still at risk are shown for each time point in the diagrams. (A) BCG-treated patients with basal level of NOS-gene activity showed a significantly better cancer specific survival (Log-rank test: p=0.037), than BCG-treated patients with increased NOS2 and decreased NOS3-gene activity. (B) The difference in risk of disease progression between the two groups of BCG-treated patients with and without basal level of NOS-gene activity was non-significant (Log-rank test: p=0.196). (C) BCG-treated patients with basal level of NOS-gene activity had a significantly lower risk of recurrence (Log-rank test: p=0.035), than BCG-treated patients with increased NOS2 and decreased NOS3-gene activity.
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f0005: Difference in survival after BCG-treatment. Comparison within the group of the BCG-treated patients (n=51), between those with at least one of the NOS2(CCTTT)non-L-carrier, NOS3-rs2070744(TT) or rs1799983(GG) considered to yield basal levels of NO (i.e. neither increased NOS2 gene activity, nor decreased NOS3 gene activity) (n=36/51; 70.6%; Basal level NO), and those with the NOS2(CCTTT)L-carrier, NOS3- rs2070744(CT/CC) and rs1799983(GT/TT) genotypes, who in theory have increased NOS2 gene activity and decreased activity in the NOS3 gene (n=15/51; 29.4%; High/low NO). Patients still at risk are shown for each time point in the diagrams. (A) BCG-treated patients with basal level of NOS-gene activity showed a significantly better cancer specific survival (Log-rank test: p=0.037), than BCG-treated patients with increased NOS2 and decreased NOS3-gene activity. (B) The difference in risk of disease progression between the two groups of BCG-treated patients with and without basal level of NOS-gene activity was non-significant (Log-rank test: p=0.196). (C) BCG-treated patients with basal level of NOS-gene activity had a significantly lower risk of recurrence (Log-rank test: p=0.035), than BCG-treated patients with increased NOS2 and decreased NOS3-gene activity.
Mentions: Analyses of genotypes only within the group of BCG-treated patients (n=51) show that those (n=36; 70.6%) with at least one of either (1) NOS2 (CCTTT)non-L-carrier (homozygous), (2) NOS3- rs2070744 (TT) or (3) rs1799983 (GG) genotypes had a significantly better cancer specific survival (HR: 0.20; CI: 0.05–0.85; p=0.029; Log-rank test: p=0.037), and a decreased risk of recurrence (HR: 0.54; CI: 0.23–1.27; p=0.160; Log-rank test: p=0.035), than patients without these three genotypes (Fig. 1).

Bottom Line: 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.Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment.

View Article: PubMed Central - PubMed

Affiliation: Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Urology, Karolinska University Hospital, 171 76 Stockholm, Sweden. Electronic address: charlotta.ryk@ki.se.

No MeSH data available.


Related in: MedlinePlus