Alakus H, Mönig SP, Warnecke-Eberz U, Alakus G, Winde G, Drebber U, Schmitz KJ, Schmid KW, Riemann K, Siffert W, Bollschweiler E, Hölscher AH, Metzger R. Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer. World J Gastroenterol 2009; 15(48): 6061-6067 [PMID: 20027678 DOI: 10.3748/wjg.15.6061]
Corresponding Author of This Article
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
Article-Type of This Article
Brief Article
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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
Abstract
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.
