Artikel
Overall- and Relapse-free Survival in Oro- and Hypoharyngeal SCC correlate with the genotype of the T393C polymorphism of the Gαs gene
Suche in Medline nach
Autoren
-
Goetz Lehnerdt
- Klinik für Hals-Nasen-Ohren-Heilkunde, Universität Duisburg-Essen, Germany
-
Peter Franz
- Klinik für Hals-Nasen-Ohren-Heilkunde, Universität Duisburg-Essen, Germany
-
Anwar Zaqoul
- Klinik für Hals-Nasen-Ohren-Heilkunde, Universität Duisburg-Essen, Germany
-
Stephan Lang
- Klinik für Hals-Nasen-Ohren-Heilkunde, Universität Duisburg-Essen, Germany
-
Kurt Werner Schmid
- Institut für Pathologie und Neuropathologie, Universität Duisburg-Essen, Germany
-
Winfried Siffert
- Institut für Pharmakogenetik, Universität Duisburg-Essen, Germany
-
Klaus Jahnke
- Klinik für Hals-Nasen-Ohren-Heilkunde, Universität Duisburg-Essen, Germany
-
Ulrich Frey
- Abteilung für Anästhesie, Universität Duisburg-Essen, Germany
| Veröffentlicht: | 8. August 2007 |
|---|
Gliederung
Text
Background: In preliminary studies we could demonstrate that the T-allele of a specific Single Nucleotide Polymorphism (SNP) in the Gαs gene (T393C) correlates with increased Gαs expression and hence apoptosis. The T-allele therefore represents a potential factor with regard to carcinogenesis, progression, and therapeutical response.
Methods: Objective of the study was the evaluation of the prognostic value of the T393C SNP in an unselected series of non palliative oro- and hypopharyngeal squamous cell carcinoma (SCC) including all tumour stages and therapeutical regimens. Genotyping was performed from paraffin-embedded tumour tissue samples from the years 1995-2001 by means of restriction analysis. Genotypes were then correlated with the clinical outcome parameters.
Results: The median follow-up of the 202 patients (162♂: 40♀) was 38 (1-133) months. Genotype frequencies (TT=24%, CT=44%, CC=32%) were not significantly different from those of a matched control sample, which makes an association between the T393C SNP and a predisposition for the analysed tumors unlikely. However, we observed a significant genotype dependent treatment-free interval with an apparent gene-dose effect (p=0.0141). GNAS1 393C homozygous patients displayed a higher risk for disease progression than T393 homozygous patients (CC versus TT: 1.9, 95% CI 1.1-3.2, p=0.019). The same genotype effect was true for overall survival: CC genotypes were at higher risk for death compared to TT genotypes (hazard ratio 1.7, 95% CI 1.1-2.9, p=0.01547).
Conclusion: The T393C SNP turns out to be a genetic tumour marker to predict the clinical course of patients suffering from oro- and hypopharyngeal cancer.
References
- 1.
- Frey UH, Eisenhardt A, Lummen G, Rubben H, Jockel KH, Schmid KW, Siffert W. The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:871-7.
- 2.
- Frey UH, Alakus H, Wohlschlaeger J, Schmitz KJ, Winde G, van Calker HG, Jockel KH, Siffert W, Schmid KW. GNAS1 T393C polymorphism and survival in patients with sporadic colorectal cancer. Clin Cancer Res. 2005;11:5071-77.
- 3.
- Frey UH, Lummen G, Jager T, Jockel KH, Schmid KW, Rubben H, Muller N, Siffert W, Eisenhardt A. The GNAS1 T393C polymorphism predicts survival in patients with clear cell renal cell carcinoma. Clin Cancer Res. 2006;12:759-63.
