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©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Dec 28, 2009; 15(48): 6061-6067
Published online Dec 28, 2009. doi: 10.3748/wjg.15.6061
Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer
Hakan Alakus, Stefan P Mönig, Ute Warnecke-Eberz, Gül Alakus, Günther Winde, Uta Drebber, Klaus J Schmitz, Kurt W Schmid, Kathrin Riemann, Winfried Siffert, Elfriede Bollschweiler, Arnulf H Hölscher, Ralf Metzger
Hakan Alakus, Stefan P Mönig, Ute Warnecke-Eberz, Elfriede Bollschweiler, Arnulf H Hölscher, Ralf Metzger, Department of General, Visceral and Cancer Surgery, Center for Integrated Oncology, University of Cologne, D-50937 Cologne, Germany
Gül Alakus, Günther Winde, Department of Gastrointestinal Surgery, Klinikum Herford, D-32049 Herford, Germany
Uta Drebber, Institute of Pathology, University of Cologne, D-50937 Cologne, Germany
Klaus J Schmitz, Kurt W Schmid, Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, D-45122 Essen, Germany
Kathrin Riemann, Winfried Siffert, Institute of Pharmacogenetics, University Hospital of Essen, University of Duisburg-Essen, D-45122 Essen, Germany
Author contributions: Alakus H was involved in the majority of experiments, in statistical analysis, in writing the manuscript and in providing financial support; Mönig SP contributed to the acquisition of surgical and routine histopathologic data; Warnecke-Eberz U performed the majority of experiments; Bollschweiler E performed statistical analysis and contributed to the conception and design of the manuscript; Metzger R and Hölscher AH performed the study, edited the manuscript and coordinated the study; Winde G was the main initiator for the study together with Alakus G who performed data and human material collection; Drebber U, Schmitz KJ and Schmid KW were responsible for pathological assessment of the resected tumor samples and for editing the manuscript; Riemann K and Siffert W built up the database of the healthy reference group, performed genotyping of this group and edited the manuscript.
Supported by The Köln Fortune Program, the CIO/Faculty of Medicine, University of Cologne and the Hoff’sche Stiftung
Correspondence to: Ralf Metzger, MD, Department of General, Visceral and Cancer Surgery, Center for Integrated Oncology, University Hospital of Cologne, Kerpener Str. 62, D-50937 Cologne, Germany. ralf.metzger@uk-koeln.de
Telephone: +49-221-4785453 Fax: +49-221-4786258
Received: September 16, 2009
Revised: October 14, 2009
Accepted: October 21, 2009
Published online: December 28, 2009
AIM: To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer.
METHODS: Genomic DNA was extracted from paraffin-embedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals. Allelic discrimination was performed by quantitative real-time polymerase chain reaction. Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression.
RESULTS: Thirty-nine (32%) patients displayed a CC genotype, 57 (46.7%) a CT genotype and 26 (21.3%) a TT genotype. The frequency of the C allele (fC) in the patient group was 0.55, which was not significantly different from that of healthy blood donors. The distribution was compatible with the Hardy-Weinberg equilibrium. Analysis of clinicopathological parameters did not show any significant correlation of the T393C genotype with gender (P = 0.50), differentiation (P = 0.29), pT-category (P = 0.19), pN-category (P = 0.30), pM-category (P = 0.25), R-category (P = 0.95), the classifications according to WHO (P = 0.34), Laurén (P = 0.16), Goseki (P = 1.00) and Ming (P = 0.74). Dichotomization between C+ (CC+CT) and C-genotypes (TT), however, revealed significantly more advanced tumor stages (P = 0.023) and lower survival rates (P = 0.043) for C allele carriers.
CONCLUSION: The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers.
