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

Abstract

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 KaplanMeier 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), pMcategory (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.

The T393C polymorphism of GNAS1 as a predictor for chemotherapy sensitivity and survival in advanced non-small-cell lung cancer patients treated with gemcitabine plus platinum

“…In this study for NSCLC, together with other studies in bladder cancer [8], clear cell renal carcinoma [14], colorectal cancer [15], and gastric cancer [16], we showed signiWcantly higher survival rate for TT genotype. However, in the invasive breast cancer [7] and intrahepatic cholangiocarcinoma [17], the CC genotype patients had more favorable clinical course.…”

Specific changes in the expression of imprinted genes in prostate cancer—implications for cancer progression and epigenetic regulation

“…Homozygosity for the GNAS T393C polymorphism, which correlated with increased G sa levels, was linked to a more favourable clinical course in bladder and colorectal cancer, as compared to patients with TC or CC genotypes. 240,241 Similarly, in clear cell renal cell carcinoma and gastric cancer, 242 homozygous CC patients were found to be at highest risk for progression. 242,243 In prostate cancer, no effect of this polymorphism could be found.…”

Are centenarians genetically predisposed to lower disease risk?

“…Hypertension (Jeunemaitre et al 1992) and CAD severity Tumor development and prognosis in several types of tumours (Alakus et al 2009;Lehnerdt et al 2008;Frey et al 2005aFrey et al , b, 2006 0 = TT, 1 = CT, 2 = CC…”