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Cellular Oncology
Published in: Cellular Oncology 4/2011

01-08-2011 | Original Paper

The GNAS1 T393C single nucleotide polymorphism predicts the natural postoperative course of complete resected esophageal cancer

Authors: Yogesh Kumar Vashist, Asad Kutup, Safije Musici, Emre F. Yekebas, Sormeh Mina, Guentac Uzunoglu, Oliver Zehler, Alexandra Koenig, Guelle Cataldegirmen, Maximillian Bockhorn, Katharina Effenberger, Viacheslav Kalinin, Klaus Pantel, Jakob R. Izbicki

Published in: Cellular Oncology | Issue 4/2011

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Abstract

Background

Genetic variations in cancer patients may serve as important prognostic indicators of clinical outcome. The GNAS1 T393C single nucleotide polymorphism (SNP) diversely correlates with the clinical outcome in cancer. The aim of this study was to evaluate the potential prognostic value of T393C-SNP in complete resected only surgically treated esophageal cancer (EC).

Methods

Genomic DNA was extracted from peripheral blood leucocytes of 190 patients who underwent only complete surgical resection for EC. T393C-SNP was correlated with clinic-pathological parameters, tumor cell dissemination in bone marrow (DTC) and clinical outcome.

Results

T-allele carriers had more advanced disease due to presence of lymph node metastasis (P < 0.0001) and DTC (P = 0.01) and higher recurrence rate (P = 0.01) compared to CC genotype. The disease-free (P < 0.001) and overall survival (P < 0.001) was better in CC compared to TT and TC patients. In the multivariate Cox regression disease-stage adjusted analysis the T393C-SNP was identified as a strong independent prognostic factor for recurrence (hazard ratio 1.8, P = 0.01) and survival (hazard ratio 2.5, P < 0.001) in EC patients.

Conclusion

Determination of T393C-SNP preoperatively will allow allocation of EC patients into different risk profiles which may help to stratify patients eligible for neoadjuvant and or adjuvant therapy.
Literature
1.
R.A. Malthaner, R.K. Wong, R.B. Rumble, L. Zuraw, Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a clinical practice guideline. BMC Cancer 4, 67 (2004)PubMedCrossRef
2.
R.A. Malthaner, R.K. Wong, R.B. Rumble, L. Zuraw, Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review and meta-analysis. BMC Med. 2, 35 (2004)PubMedCrossRef
3.
C.G. Peyre, J.A. Hagen, S.R. DeMeester, J.J. Van Lanschot, A. Holscher et al., Predicting systemic disease in patients with esophageal cancer after esophagectomy: a multinational study on the significance of the number of involved lymph nodes. Ann. Surg. 248, 979–985 (2008)PubMedCrossRef
4.
E. Adjadj, M. Schlumberger, F. de Vathaire, Germ-line DNA polymorphisms and susceptibility to differentiated thyroid cancer. Lancet Oncol. 10, 181–190 (2009)PubMedCrossRef
5.
D.F. Easton, K.A. Pooley, A.M. Dunning, P.D. Pharoah, D. Thompson et al., Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447, 1087–1093 (2007)PubMedCrossRef
6.
7.
8.
L.S. Weinstein, S. Yu, D.R. Warner, J. Liu, Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting. Endocr. Rev. 22, 675–705 (2001)PubMedCrossRef
9.
J. Lyons, C.A. Landis, G. Harsh, L. Vallar, K. Grunewald et al., Two G protein oncogenes in human endocrine tumors. Science 249, 655–659 (1990)PubMedCrossRef
10.
A. Lania, G. Mantovani, A. Spada, Genetics of pituitary tumors: focus on G-protein mutations. Exp. Biol. Med. (Maywood) 228, 1004–1017 (2003)
11.
Y. Daaka, L.M. Luttrell, R.J. Lefkowitz, Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. Nature 390, 88–91 (1997)PubMedCrossRef
12.
X. Yang, F.Y. Lee Sr., G.S. Wand, Increased expression of Gs(alpha) enhances activation of the adenylyl cyclase signal transduction cascade. Mol. Endocrinol. 11, 1053–1061 (1997)PubMedCrossRef
13.
U.H. Frey, H. Alakus, J. Wohlschlaeger, K.J. Schmitz, G. Winde et al., GNAS1 T393C polymorphism and survival in patients with sporadic colorectal cancer. Clin. Cancer Res. 11, 5071–5077 (2005)PubMedCrossRef
14.
U.H. Frey, A. Eisenhardt, G. Lummen, H. Rubben, K.H. Jockel et al., The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer. Cancer Epidemiol. Biomark. Prev. 14, 871–877 (2005)CrossRef
15.
K. Pantel, C. Alix-Panabieres, S. Riethdorf, Cancer micrometastases. Nat Rev Clin Oncol 6, 339–351 (2009)PubMedCrossRef
16.
K. Pantel, R.H. Brakenhoff, B. Brandt, Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat. Rev. Cancer 8, 329–340 (2008)PubMedCrossRef
17.
E. Borgen, B. Naume, J.M. Nesland, G. Kvalheim, K. Beiske et al., Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. Establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy 1, 377–388 (1999)PubMedCrossRef
18.
T. Fehm, S. Braun, V. Muller, W. Janni, G. Gebauer et al., A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer 107, 885–892 (2006)PubMedCrossRef
19.
U.H. Frey, G. Lummen, T. Jager, K.H. Jockel, K.W. Schmid et al., The GNAS1 T393C polymorphism predicts survival in patients with clear cell renal cell carcinoma. Clin. Cancer Res. 12, 759–763 (2006)PubMedCrossRef
20.
U.H. Frey, H. Nuckel, L. Sellmann, D. Siemer, R. Kuppers et al., The GNAS1 T393C polymorphism is associated with disease progression and survival in chronic lymphocytic leukemia. Clin. Cancer Res. 12, 5686–5692 (2006)PubMedCrossRef
21.
G.F. Lehnerdt, P. Franz, S. Winterhoff, A. Bankfalvi, S. Grehl et al., The GNAS1 T393C polymorphism predicts survival in patients with advanced squamous cell carcinoma of the larynx. Laryngoscope 118, 2172–2176 (2008)PubMedCrossRef
22.
G.F. Lehnerdt, P. Franz, A. Zaqoul, K.J. Schmitz, S. Grehl et al., Overall and relapse-free survival in oropharyngeal and hypopharyngeal squamous cell carcinoma are associated with genotypes of T393C polymorphism of the GNAS1 gene. Clin. Cancer Res. 14, 1753–1758 (2008)PubMedCrossRef
23.
L.S. Weinstein, J. Liu, A. Sakamoto, T. Xie, M. Chen, Minireview: GNAS: normal and abnormal functions. Endocrinology 145, 5459–5464 (2004)PubMedCrossRef
24.
F. Capon, M.H. Allen, M. Ameen, A.D. Burden, D. Tillman et al., A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum. Mol. Genet. 13, 2361–2368 (2004)PubMedCrossRef
25.
J. Duan, M.S. Wainwright, J.M. Comeron, N. Saitou, A.R. Sanders et al., Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum. Mol. Genet. 12, 205–216 (2003)PubMedCrossRef
26.
M.J. Tierney, R.L. Medcalf, Plasminogen activator inhibitor type 2 contains mRNA instability elements within exon 4 of the coding region. Sequence homology to coding region instability determinants in other mRNAs. J. Biol. Chem. 276, 13675–13684 (2001)PubMed
27.
F. Otterbach, R. Callies, U.H. Frey, K.J. Schmitz, C. Wreczycki et al., The T393C polymorphism in the gene GNAS1 of G protein is associated with survival of patients with invasive breast carcinoma. Breast Cancer Res. Treat. 105, 311–317 (2007)PubMedCrossRef
28.
K.J. Schmitz, H. Lang, U.H. Frey, G.C. Sotiropoulos, J. Wohlschlaeger et al., GNAS1 T393C polymorphism is associated with clinical course in patients with intrahepatic cholangiocarcinoma. Neoplasia 9, 159–165 (2007)PubMedCrossRef
29.
H. Alakus, U. Warnecke-Eberz, E. Bollschweiler, S.P. Monig, D. Vallbohmer et al., GNAS1 T393C polymorphism is associated with histopathological response to neoadjuvant radiochemotherapy in esophageal cancer. Pharmacogenomics J. 9, 202–207 (2009)PubMedCrossRef
30.
E.J. Neer, Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80, 249–257 (1995)PubMedCrossRef
31.
L.S. Weinstein, T. Xie, Q.H. Zhang, M. Chen, Studies of the regulation and function of the Gs alpha gene Gnas using gene targeting technology. Pharmacol. Ther. 115, 271–291 (2007)PubMedCrossRef
32.
A. Harry, Y. Chen, R. Magnusson, R. Iyengar, G. Weng, Differential regulation of adenylyl cyclases by Galphas. J. Biol. Chem. 272, 19017–19021 (1997)PubMedCrossRef
33.
M. Keiper, M.B. Stope, D. Szatkowski, A. Bohm, K. Tysack et al., Epac- and Ca2+ -controlled activation of Ras and extracellular signal-regulated kinases by Gs-coupled receptors. J. Biol. Chem. 279, 46497–46508 (2004)PubMedCrossRef
34.
S. Kiermayer, R.M. Biondi, J. Imig, G. Plotz, J. Haupenthal et al., Epac activation converts cAMP from a proliferative into a differentiation signal in PC12 cells. Mol. Biol. Cell 16, 5639–5648 (2005)PubMedCrossRef
35.
C. Peyssonnaux, A. Eychene, The Raf/MEK/ERK pathway: new concepts of activation. Biol. Cell 93, 53–62 (2001)PubMedCrossRef
36.
B.C. Visser, A.P. Venook, M.G. Patti, Adjuvant and neoadjuvant therapy for esophageal cancer: a critical reappraisal. Surg. Oncol. 12, 1–7 (2003)PubMedCrossRef
37.
J. Zhang, H.Q. Chen, Y.W. Zhang, J.Q. Xiang, Adjuvant chemotherapy in oesophageal cancer: a meta-analysis and experience from the Shanghai Cancer Hospital. J. Int. Med. Res. 36, 875–882 (2008)PubMed
38.
A. DeMichele, R. Aplenc, J. Botbyl, T. Colligan, L. Wray et al., Drug-metabolizing enzyme polymorphisms predict clinical outcome in a node-positive breast cancer cohort. J. Clin. Oncol. 23, 5552–5559 (2005)PubMedCrossRef
39.
F. Innocenti, L. Iyer, M.J. Ratain, Pharmacogenetics: a tool for individualizing antineoplastic therapy. Clin. Pharmacokinet. 39, 315–325 (2000)PubMedCrossRef
40.
F. Innocenti, S.D. Undevia, L. Iyer, P.X. Chen, S. Das et al., Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J. Clin. Oncol. 22, 1382–1388 (2004)PubMedCrossRef
41.
P.E. Huijts, M.P. Vreeswijk, K.H. Kroeze-Jansema, C.E. Jacobi, C. Seynaeve et al., Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases. Breast Cancer Res. 9, R78 (2007)PubMedCrossRef
42.
P. Kraft, P. Pharoah, S.J. Chanock, D. Albanes, L.N. Kolonel et al., Genetic variation in the HSD17B1 gene and risk of prostate cancer. PLoS Genet. 1, e68 (2005)PubMedCrossRef
43.
U.H. Frey, A. Fritz, S. Rotterdam, K.W. Schmid, A. Potthoff et al., GNAS1 T393C polymorphism and disease progression in patients with malignant melanoma. Eur. J. Med. Res. 15, 422–427 (2010)PubMed
Metadata
Title
The GNAS1 T393C single nucleotide polymorphism predicts the natural postoperative course of complete resected esophageal cancer
Authors
Yogesh Kumar Vashist
Asad Kutup
Safije Musici
Emre F. Yekebas
Sormeh Mina
Guentac Uzunoglu
Oliver Zehler
Alexandra Koenig
Guelle Cataldegirmen
Maximillian Bockhorn
Katharina Effenberger
Viacheslav Kalinin
Klaus Pantel
Jakob R. Izbicki
Publication date
01-08-2011
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 4/2011
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-011-0016-x

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