Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer

• Published in: World journal of gastroenterology : WJG Vol. 15; no. 48; pp. 6061 - 6067
• Main Authors: Alakus, Hakan, Mönig, Stefan P, Warnecke-Eberz, Ute, Alakus, Gül, Winde, Günther, Drebber, Uta, Schmitz, Klaus J, Schmid, Kurt W, Riemann, Kathrin, Siffert, Winfried, Bollschweiler, Elfriede, Hölscher, Arnulf H, Metzger, Ralf
• Format: Journal Article
• Language: English
• Published: United States Department of General, Visceral and Cancer Surgery, Center for Integrated Oncology, University of Cologne, D-50937 Cologne, Germany%Department of Gastrointestinal Surgery, Klinikum Herford, D-32049 Herford, Germany Uta Drebber, Institute of Pathology, University of Cologne,D-50937 Cologne, Germany%Institute of Pathology, University of Cologne,D-50937 Cologne, Germany%Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, D-45122 Essen, Germany%Institute of Pharmacogenetics, University Hospital of Essen, University of Duisburg-Essen, D-45122 Essen, Germany 28-12-2009; The WJG Press and Baishideng
• Subjects: Adult; Aged; Aged, 80 and over; Brief; Carcinoma - diagnosis; Carcinoma - genetics; Carcinoma - mortality; Chromogranins; Female; Genotype; Germany - epidemiology; GTP-Binding Protein alpha Subunits, Gs - genetics; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Stomach Neoplasms - diagnosis; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Survival Analysis; 多态性; Tumor stage; Prognosis; Gastric cancer; G Protein; Polymorphism
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.15.6061

AIM： To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer. METHODS： Genomic DNA was extracted from paraffinembedded 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）, Lauren （P = 0.16）, Goseki （P = 1.00） and Ming （P =0.74）. Dichotomization between C＋ （CC＋CT） and C-genotypes （FI）, 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.