The GNAS1 T393C polymorphism predicts survival in patients with clear cell renal cell carcinoma.

Abstract

PURPOSE:

G proteins mediate signaling from cell surface receptors to specific intracellular proteins. In vitro cancer cell line studies revealed a link between the Galphas protein and proapoptotic processes. We have recently shown that TT genotypes of the GNAS1 T393C polymorphism display increased transcription of Galphas and a more favorable clinical course in bladder and colorectal cancer patients compared both with TC or CC genotypes.

EXPERIMENTAL DESIGN:

In the present study, 150 patients with clear cell renal cell carcinoma surgically treated by nephrectomy with curative intent were retrospectively genotyped to elucidate a potential association between T393C genotypes and clinical outcome.

RESULTS:

The C-allele frequency in the renal cell carcinoma patient group was 0.51, which is not significantly different from that of a healthy blood donor group. Kaplan-Meier curves for tumor progression, development of metastasis, and tumor-related death showed a significant association of the T393C polymorphism with outcome (5-year cancer-specific survival rates: TT, 91%; TC, 81%; CC, 69%; P = 0.015). Multivariate Cox proportional analysis of a 10-year follow-up confirmed the T393C polymorphism as an independent prognostic factor in clear cell renal cell carcinoma. Homozygous CC patients were at highest risk for progression (hazard ratio, 2.48; P = 0.009) or tumor-related death (hazard ratio, 3.15; P = 0.018) compared with T-allele carriers.

CONCLUSION:

Our results show that besides tumor stage, lymph node status, and tumor grade, the GNAS1 T393C status is a novel independent host factor for disease progression in patients with clear cell renal cell carcinoma and provides further evidence for the T393C polymorphism as a general prognostic tumor marker.

• Authors: Ulrich H Frey, Gerd Lümmen, Tobias Jäger, Karl-Heinz Jöckel, Kurt W Schmid, Herbert Rübben, Norbert Müller, Winfried Siffert, Andreas Eisenhardt
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 3 Pt 1 Pg. 759-63 (Feb 01 2006) ISSN: 1078-0432 [Print] United States
• PMID: 16467086 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Chromogranins
• GNAS protein, human
• GTP-Binding Protein alpha Subunits, Gs

Topics

• Carcinoma, Renal Cell (diagnosis, genetics, surgery)
• Chromogranins
• Disease Progression
• Female
• Follow-Up Studies
• GTP-Binding Protein alpha Subunits, Gs (genetics)
• Gene Expression Regulation, Neoplastic
• Genotype
• Humans
• Kidney Neoplasms (diagnosis, genetics, surgery)
• Male
• Middle Aged
• Nephrectomy (methods)
• Polymorphism, Genetic
• Prognosis
• Proportional Hazards Models
• Retrospective Studies
• Survival Analysis