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

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 signif icantly different from that of healthy blood donors.The distribution was compatible with the Hardy-Weinberg equilibrium.Analysis of clinicopathological parameters did not show any signif icant 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 signif icantly 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.