This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frey, U. H. Articles by Schmid, K. W. Search for Related Content PubMed PubMed Citation Articles by Frey, U. H. Articles by Schmid, K. W.

GNAS1 T393C Polymorphism and Survival in Patients with Sporadic Colorectal Cancer

Authors' Affiliations: ¹ Institute of Pharmacology, ² Institute of Pathology, and ³ Institute of Medical Informatics, Biometry, and Epidemiology, University Hospital of Essen, Essen, Germany and ⁴ Department of Gastrointestinal Surgery and ⁵ Institute of Pathology, Klinikum Herford, Herford, Germany

Requests for reprints: Ulrich H. Frey, Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany. Phone: 49-201-7233459; Fax: 49-201-7235968; E-mail: Ulrich.Frey{at}uni-essen.de.

Purpose: Signaling via the G protein Gs pathway is linked to proapoptotic processes in cancer cell lines. We have recently shown an association between the GNAS1 T393C polymorphism and disease progression in patients with bladder cancer with homozygous TT genotypes displaying increased transcription of Gs and a more favorable clinical course compared with C-allele carriers.

Experimental Design: In the present study, 151 patients with sporadic colorectal cancer were retrospectively genotyped to examine a potential association between T393C genotypes and survival. Moreover, two other single-nucleotide polymorphisms in common haplotype blocks within the gene GNAS1 and their interaction with the T393C polymorphism were investigated.

Results: The allele frequency in the patients group was not significantly different from that of healthy blood donors. Kaplan-Meier curves for overall survival (mean follow-up, 43 months) showed that in International Union Against Cancer (UICC) stages I to II, the 5-year survival rate was significantly higher in TT genotypes (87.8%) compared with TC (71.0%) and CC genotypes (50.0%; P = 0.009), whereas no genotype effect could be observed for UICC stages III to IV. In multivariate Cox proportional analysis the T393C polymorphism was an independent prognostic factor for survival. Homozygous CC patients were at highest risk for death (hazard ratio, 12.1; P = 0.006) compared with TT genotypes. Heterozygous patients had an intermediate risk compatible with a gene-dose effect. The two haplotype blocks investigated were not associated with clinical outcome.

Conclusions: The results support the role of the T393C polymorphism as a marker for survival in patients with colorectal cancer stages I to II and in the identification of patients who may benefit from adjuvant chemotherapy.

This article has been cited by other articles:

				G. F. Lehnerdt, P. Franz, A. Zaqoul, K. J. Schmitz, S. Grehl, S. Lang, K. W. Schmid, W. Siffert, K. Jahnke, and U. H. Frey Overall and Relapse-Free Survival in Oropharyngeal and Hypopharyngeal Squamous Cell Carcinoma Are Associated with Genotypes of T393C Polymorphism of the GNAS1 Gene Clin. Cancer Res., March 15, 2008; 14(6): 1753 - 1758. [Abstract] [Full Text] [PDF]

				S. Hahn, U. H Frey, W. Siffert, S. Tan, K. Mann, and O. E Janssen The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome. Eur. J. Endocrinol., November 1, 2006; 155(5): 763 - 770. [Abstract] [Full Text] [PDF]

				U. H. Frey, H. Nuckel, L. Sellmann, D. Siemer, R. Kuppers, J. Durig, U. Duhrsen, and W. Siffert The GNAS1 T393C Polymorphism Is Associated with Disease Progression and Survival in Chronic Lymphocytic Leukemia. Clin. Cancer Res., October 1, 2006; 12(19): 5686 - 5692. [Abstract] [Full Text] [PDF]

				U. H. Frey, G. Lummen, T. Jager, K.-H. Jockel, K. W. Schmid, H. Rubben, N. Muller, W. Siffert, and A. Eisenhardt The GNAS1 T393C Polymorphism Predicts Survival in Patients with Clear Cell Renal Cell Carcinoma Clin. Cancer Res., February 1, 2006; 12(3): 759 - 763. [Abstract] [Full Text] [PDF]