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


CONCLUSIONS
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.
Alakus
Hakan
H
Department of General, Visceral and Cancer Surgery, Center for Integrated Oncology, University Hospital of Cologne, Kerpener Str. 62, D-50937 Cologne, Germany.
Mönig
Stefan P
SP
Warnecke-Eberz
Ute
U
Alakus
Gül
G
Winde
Günther
G
Drebber
Uta
U
Schmitz
Klaus J
KJ
Schmid
Kurt W
KW
Riemann
Kathrin
K
Siffert
Winfried
W
Bollschweiler
Elfriede
E
Hölscher
Arnulf H
AH
Metzger
Ralf
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D002864:Chromogranins; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis
D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs