G2Cdb::Human Disease report

Disease id
D00000062
Name
Transitional cell carcinoma of the bladder
Nervous system disease
no

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001473 GNAS
GNAS complex locus
Y (15824158) Single nucleotide polymorphism (SNP) Y

References

  • The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer.

    Frey UH, Eisenhardt A, Lümmen G, Rübben H, Jöckel KH, Schmid KW and Siffert W

    Institut für Pharmakologie, Universitätsklinikum, Essen, Hufelandstrasse 55, D-45122 Essen, Germany. Ulrich.Frey@uni-essen.de

    The G protein G(alpha)s pathway is linked to proapoptotic signaling in cancer cell lines. To assess the role of the GNAS1 locus encoding G(alpha)s as a genetic factor for disease progression of transitional cell carcinoma (TCC) of the bladder, we genotyped the synonymous T393C polymorphism in 254 patients with TCC (minor allele frequency: 0.43) to examine a potential association between genotypes and disease progression. Using Kaplan-Meier estimates to calculate 5-year probabilities of follow-up, we could show that progression-free survival, metastasis-free survival, and cancer-specific survival was significantly increased in TT genotypes (56%, 84%, 82%) compared with CC genotypes (35%, 53%, 58%). In multivariate Cox proportional hazard analysis, the T393C polymorphism was an independent prognostic factor for clinical outcome. Homozygous CC patients were at highest risk for progression [odds ratio (OR), 1.94; P = 0.020], metastasis (OR, 3.49; P = 0.005), and tumor-related death (OR, 2.49; P = 0.031) compared with TT genotypes. Heterozygous patients had an intermediate risk compatible with a gene-dose effect. Real-time PCR analysis of urothelial tumor tissue as well as adipose and heart tissue revealed that G(alpha)s mRNA expression was highest in TT genotypes, indicating a proapoptotic effect in these genotypes. In conclusion, the GNAS1 T393C status associated with differential G(alpha)s mRNA expression is a novel independent prognostic marker for clinical outcome supporting a functional role of G(alpha)s in bladder cancer progression.

    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2005;14;4;871-7

Literature (1)

Pubmed - human_disease

  • The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer.

    Frey UH, Eisenhardt A, Lümmen G, Rübben H, Jöckel KH, Schmid KW and Siffert W

    Institut für Pharmakologie, Universitätsklinikum, Essen, Hufelandstrasse 55, D-45122 Essen, Germany. Ulrich.Frey@uni-essen.de

    The G protein G(alpha)s pathway is linked to proapoptotic signaling in cancer cell lines. To assess the role of the GNAS1 locus encoding G(alpha)s as a genetic factor for disease progression of transitional cell carcinoma (TCC) of the bladder, we genotyped the synonymous T393C polymorphism in 254 patients with TCC (minor allele frequency: 0.43) to examine a potential association between genotypes and disease progression. Using Kaplan-Meier estimates to calculate 5-year probabilities of follow-up, we could show that progression-free survival, metastasis-free survival, and cancer-specific survival was significantly increased in TT genotypes (56%, 84%, 82%) compared with CC genotypes (35%, 53%, 58%). In multivariate Cox proportional hazard analysis, the T393C polymorphism was an independent prognostic factor for clinical outcome. Homozygous CC patients were at highest risk for progression [odds ratio (OR), 1.94; P = 0.020], metastasis (OR, 3.49; P = 0.005), and tumor-related death (OR, 2.49; P = 0.031) compared with TT genotypes. Heterozygous patients had an intermediate risk compatible with a gene-dose effect. Real-time PCR analysis of urothelial tumor tissue as well as adipose and heart tissue revealed that G(alpha)s mRNA expression was highest in TT genotypes, indicating a proapoptotic effect in these genotypes. In conclusion, the GNAS1 T393C status associated with differential G(alpha)s mRNA expression is a novel independent prognostic marker for clinical outcome supporting a functional role of G(alpha)s in bladder cancer progression.

    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2005;14;4;871-7

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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