BACKGROUND: Genetic variations in cancer patients may serve as important prognostic indicators of clinical outcome. The GNAS1 T393C single nucleotide polymorphism (SNP) diversely correlates with the clinical outcome in cancer. The aim of this study was to evaluate the potential prognostic value of T393C-SNP in complete resected only surgically treated esophageal cancer (EC). METHODS: Genomic DNA was extracted from peripheral blood leucocytes of 190 patients who underwent only complete surgical resection for EC. T393C-SNP was correlated with clinic-pathological parameters, tumor cell dissemination in bone marrow (DTC) and clinical outcome. RESULTS: T-allele carriers had more advanced disease due to presence of lymph node metastasis (P < 0.0001) and DTC (P = 0.01) and higher recurrence rate (P = 0.01) compared to CC genotype. The disease-free (P < 0.001) and overall survival (P < 0.001) was better in CC compared to TT and TC patients. In the multivariate Cox regression disease-stage adjusted analysis the T393C-SNP was identified as a strong independent prognostic factor for recurrence (hazard ratio 1.8, P = 0.01) and survival (hazard ratio 2.5, P < 0.001) in EC patients. CONCLUSION: Determination of T393C-SNP preoperatively will allow allocation of EC patients into different risk profiles which may help to stratify patients eligible for neoadjuvant and or adjuvant therapy.
BACKGROUND: Genetic variations in cancerpatients may serve as important prognostic indicators of clinical outcome. The GNAS1T393C single nucleotide polymorphism (SNP) diversely correlates with the clinical outcome in cancer. The aim of this study was to evaluate the potential prognostic value of T393C-SNP in complete resected only surgically treated esophageal cancer (EC). METHODS: Genomic DNA was extracted from peripheral blood leucocytes of 190 patients who underwent only complete surgical resection for EC. T393C-SNP was correlated with clinic-pathological parameters, tumor cell dissemination in bone marrow (DTC) and clinical outcome. RESULTS: T-allele carriers had more advanced disease due to presence of lymph node metastasis (P < 0.0001) and DTC (P = 0.01) and higher recurrence rate (P = 0.01) compared to CC genotype. The disease-free (P < 0.001) and overall survival (P < 0.001) was better in CC compared to TT and TCpatients. In the multivariate Cox regression disease-stage adjusted analysis the T393C-SNP was identified as a strong independent prognostic factor for recurrence (hazard ratio 1.8, P = 0.01) and survival (hazard ratio 2.5, P < 0.001) in EC patients. CONCLUSION: Determination of T393C-SNP preoperatively will allow allocation of EC patients into different risk profiles which may help to stratify patients eligible for neoadjuvant and or adjuvant therapy.
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Authors: Ulrich H Frey; Andreas Eisenhardt; Gerd Lümmen; Herbert Rübben; Karl-Heinz Jöckel; Kurt W Schmid; Winfried Siffert Journal: Cancer Epidemiol Biomarkers Prev Date: 2005-04 Impact factor: 4.254
Authors: Ulrich H Frey; Hakan Alakus; Jeremias Wohlschlaeger; Klaus J Schmitz; Günther Winde; Hans G van Calker; Karl-Heinz Jöckel; Winfried Siffert; Kurt W Schmid Journal: Clin Cancer Res Date: 2005-07-15 Impact factor: 12.531
Authors: H Alakus; U Warnecke-Eberz; E Bollschweiler; S P Mönig; D Vallböhmer; J Brabender; U Drebber; S E Baldus; K Riemann; W Siffert; A H Hölscher; R Metzger Journal: Pharmacogenomics J Date: 2009-03-10 Impact factor: 3.550
Authors: Peter Kraft; Paul Pharoah; Stephen J Chanock; Demetrius Albanes; Laurence N Kolonel; Richard B Hayes; David Altshuler; Gerald Andriole; Christine Berg; Heiner Boeing; Noel P Burtt; Bas Bueno-de-Mesquita; Eugenia E Calle; Howard Cann; Federico Canzian; Yen-Ching Chen; David E Crawford; Alison M Dunning; Heather S Feigelson; Matthew L Freedman; John M Gaziano; Ed Giovannucci; Carlos Alberto Gonzalez; Christopher A Haiman; Goran Hallmans; Brian E Henderson; Joel N Hirschhorn; David J Hunter; Rudolf Kaaks; Timothy Key; Loic Le Marchand; Jing Ma; Kim Overvad; Domenico Palli; Malcolm C Pike; Elio Riboli; Carmen Rodriguez; Wendy V Setiawan; Meir J Stampfer; Daniel O Stram; Gilles Thomas; Michael J Thun; Ruth Travis; Antonia Trichopoulou; Jarmo Virtamo; Sholom Wacholder Journal: PLoS Genet Date: 2005-11-25 Impact factor: 5.917
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