Artikel
Overall- and Relapse-free Survival in Oro- and Hypoharyngeal SCC correlate with the genotype of the T393C polymorphism of the Gαs gene
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Veröffentlicht: | 8. August 2007 |
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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
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