Artikel
The C825T polymorphism of the G Protein β3 subunit (GNB3) is a prognostic parameter for relapse-free and overall survival of patients with HNSCC
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Autoren
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Götz Frederik Lehnerdt
- Department of Otorhinolaryngology, Essen, Germany
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Agnes Bankfalvi
- Institute of Pathology and Neuropathology, Essen, Germany
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Peter Franz
- Department of Otorhinolaryngology, Essen, Germany
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Sara Grehl
- Department of Radiotherapy at the West German Cancer Center Essen, Essen, Germany
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Stephan Lang
- Department of Otorhinolaryngology, Essen, Germany
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Kurt Werner Schmid
- Institute of Pathology and Neuropathology, Essen, Germany
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Winfried Siffert
- Institute of Pharmacogenetics, Essen, Germany
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Klaus Jahnke
- Department of Otorhinolaryngology, Essen, Germany
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Ulrich H. Frey
- Institute of Pharmacogenetics, Essen, Germany
| Veröffentlicht: | 22. Juli 2009 |
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Gliederung
Text
The T-allele of a common C825T single nucleotide polymorphism (SNP) in the gene GNB3, encoding the G 3 subunit of heterotrimeric G-proteins, is associated with a truncated form of the G 3 protein that imparts a greater signaling capacity than the alternative C-allele encoding a non-truncated protein. We analyzed the C825T-allele status with regard to disease progression in patients with head and neck squamous cell carcinoma (HNSCC). The prognostic value of the SNP was evaluated in an unselected series of 341 patients treated with curative intent for HNSCC including all tumor stages with different therapeutical regimens. Genotype analysis was performed by Pyrosequencing using DNA from paraffin-embedded tissue samples. Genotypes were correlated with relapse-free and overall survival. Proportions of 5-year relapse-free intervals were 62% for CC, 60% for TC, and 42% for TT genotypes. Kaplan-Meier curves revealed a significant genotype-dependent relapse-free interval (p=0.036). In multivariate analysis with stage, localization, grade, gender, and smoking habits as covariates GNB3 825T homozygous patients displayed a higher risk for relapse than C825 homozygous patients (TT versus CC: 2.6, 95% CI 1.4-4.8, p=0.002). The same genotype effect was found for overall survival, TT genotypes were at higher risk for death compared to CC genotypes (hazard ratio 2.6, 95% CI 1.6-4.3, p<0.001), and 5-year survival proportions were 60% for CC, 52% for TC, and 33% for TT. The GNB3 C825T SNP thus represents a host derived prognostic marker in HNSCC which allows identifying high risk patients which could benefit from novel and/or more aggressive therapeutic regimes.
