Association of the GNAS1 T393C Polymorphism with Tumor Stage and Survival in Gastric Cancer

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2009 Dec 23

PMID 20027678

Citations 7

Authors

Hakan Alakus

Stefan P Monig

Ute Warnecke-Eberz

Gul Alakus

Gunther Winde

Uta Drebber

Klaus J Schmitz

Kurt W Schmid

Kathrin Riemann

Winfried Siffert

Elfriede Bollschweiler

Arnulf H Holscher

Ralf Metzger

Affiliations

Soon will be listed here.

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.

Citing Articles

CC Genotype of GNAS c.393C>T (rs7121) Polymorphism Has a Protective Effect against Development of BK Viremia and BKV-Associated Nephropathy after Renal Transplant.

Peitz T, Mohlendick B, Eisenberger U, Siffert W, Heinemann F, Kribben A Pathogens. 2022; 11(10).

PMID: 36297195 PMC: 9609707. DOI: 10.3390/pathogens11101138.

Intronic polymorphisms in genes LRFN2 (rs2494938) and DNAH11 (rs2285947) are prognostic indicators of esophageal squamous cell carcinoma.

Wang J, Wang Q, Wei B, Zhou Y, Qian Z, Gao Y BMC Med Genet. 2019; 20(1):72.

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Relationship between GNAS1 T393C polymorphism and aseptic loosening after total hip arthroplasty.

Stelmach P, Kauther M, Fuest L, Kurscheid G, Gehrke T, Klenke S Eur J Med Res. 2017; 22(1):29.

PMID: 28830502 PMC: 5568317. DOI: 10.1186/s40001-017-0271-z.

TT genotype of GNAS1 T393C polymorphism predicts better outcome of advanced non-small cell lung cancer patients.

Gong H, Hu W, Wang X, Zhu F, Song Q World J Gastrointest Oncol. 2014; 6(12):444-9.

PMID: 25516778 PMC: 4266817. DOI: 10.4251/wjgo.v6.i12.444.

GNB3, eNOS, and mitochondrial DNA polymorphisms correlate to natural longevity in a Xinjiang Uygur population.

Nijiati M, Saidaming A, Qiao J, Cheng Z, Qiu C, Sun Y PLoS One. 2013; 8(12):e81806.

PMID: 24376503 PMC: 3869651. DOI: 10.1371/journal.pone.0081806.

References

Yang X, Lee Sr F, Wand G . Increased expression of Gs(alpha) enhances activation of the adenylyl cyclase signal transduction cascade. Mol Endocrinol. 1997; 11(8):1053-61. DOI: 10.1210/mend.11.8.9957. View

Parkin D, Pisani P, Ferlay J . Global cancer statistics. CA Cancer J Clin. 1999; 49(1):33-64, 1. DOI: 10.3322/canjclin.49.1.33. View

Brennan M . Current status of surgery for gastric cancer: a review. Gastric Cancer. 2005; 8(2):64-70. DOI: 10.1007/s10120-005-0319-6. View

Menges M . [Diagnosis, staging and therapy of gastric cancer]. Z Gastroenterol. 2004; 42(8):767-73. DOI: 10.1055/s-2004-813342. View

Frey U, Eisenhardt A, Lummen G, Rubben H, Jockel K, Schmid K . The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14(4):871-7. DOI: 10.1158/1055-9965.EPI-04-0720. View

Bollschweiler E, Breckheimer S, Monig S, Holscher A . [The prognostic relevance of age and comorbidity in patients with resected gastric cancer]. Zentralbl Chir. 2009; 134(1):71-6. DOI: 10.1055/s-2008-1076879. View

Srivastava R, Srivastave A, Cho-Chung Y . Synergistic effects of 8-Cl-cAMP and retinoic acids in the inhibition of growth and induction of apoptosis in ovarian cancer cells: induction of retinoic acid receptor beta. Mol Cell Biochem. 2000; 204(1-2):1-9. DOI: 10.1023/a:1007074814676. View

Frey U, Lummen G, Jager T, Jockel K, Schmid K, Rubben H . The GNAS1 T393C polymorphism predicts survival in patients with clear cell renal cell carcinoma. Clin Cancer Res. 2006; 12(3 Pt 1):759-63. DOI: 10.1158/1078-0432.CCR-05-1722. View

Wittekind C, Compton C, Greene F, Sobin L . TNM residual tumor classification revisited. Cancer. 2002; 94(9):2511-6. DOI: 10.1002/cncr.10492. View

10.

Otterbach F, Callies R, Frey U, Schmitz K, Wreczycki C, Kimmig R . The T393C polymorphism in the gene GNAS1 of G protein is associated with survival of patients with invasive breast carcinoma. Breast Cancer Res Treat. 2006; 105(3):311-7. DOI: 10.1007/s10549-006-9462-y. View

11.

Yan L, Herrmann V, Hofer J, Insel P . beta-adrenergic receptor/cAMP-mediated signaling and apoptosis of S49 lymphoma cells. Am J Physiol Cell Physiol. 2000; 279(5):C1665-74. DOI: 10.1152/ajpcell.2000.279.5.C1665. View

12.

Kim J, Kwon O, Oh S, Yang H . Results of surgery on 6589 gastric cancer patients and immunochemosurgery as the best treatment of advanced gastric cancer. Ann Surg. 1992; 216(3):269-78; discussion 278-9. PMC: 1242606. DOI: 10.1097/00000658-199209000-00006. View

13.

Hansson L, Sparen P, Nyren O . Survival in stomach cancer is improving: results of a nationwide population-based Swedish study. Ann Surg. 1999; 230(2):162-9. PMC: 1420858. DOI: 10.1097/00000658-199908000-00005. View

14.

Japanese Gastric Cancer Association . Japanese Classification of Gastric Carcinoma - 2nd English Edition -. Gastric Cancer. 2002; 1(1):10-24. DOI: 10.1007/s101209800016. View

15.

Frey U, Nuckel H, Sellmann L, Siemer D, Kuppers R, Durig J . The GNAS1 T393C polymorphism is associated with disease progression and survival in chronic lymphocytic leukemia. Clin Cancer Res. 2006; 12(19):5686-92. DOI: 10.1158/1078-0432.CCR-06-0288. View

16.

Frey U, Alakus H, Wohlschlaeger J, Schmitz K, Winde G, van Calker H . GNAS1 T393C polymorphism and survival in patients with sporadic colorectal cancer. Clin Cancer Res. 2005; 11(14):5071-7. DOI: 10.1158/1078-0432.CCR-05-0472. View

17.

Kwee R, Kwee T . Imaging in local staging of gastric cancer: a systematic review. J Clin Oncol. 2007; 25(15):2107-16. DOI: 10.1200/JCO.2006.09.5224. View

18.

Yasui W, Oue N, Aung P, Matsumura S, Shutoh M, Nakayama H . Molecular-pathological prognostic factors of gastric cancer: a review. Gastric Cancer. 2005; 8(2):86-94. DOI: 10.1007/s10120-005-0320-0. View

19.

Alakus H, Warnecke-Eberz U, Bollschweiler E, Monig S, Vallbohmer D, Brabender J . GNAS1 T393C polymorphism is associated with histopathological response to neoadjuvant radiochemotherapy in esophageal cancer. Pharmacogenomics J. 2009; 9(3):202-7. DOI: 10.1038/tpj.2009.5. View

20.

Schmitz K, Lang H, Frey U, Sotiropoulos G, Wohlschlaeger J, Reis H . GNAS1 T393C polymorphism is associated with clinical course in patients with intrahepatic cholangiocarcinoma. Neoplasia. 2007; 9(2):159-65. PMC: 1813929. DOI: 10.1593/neo.06796. View