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Interleukin-2 −330T>G Genetic Polymorphism Associates with Prognosis Following Surgery for Thoracic Esophageal Squamous Cell Cancer

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Key molecules in the T helper (Th)1 and Th2 pathways underlie differential responses to the progression and surgical treatment of cancer. We investigated the relationship between Th1/Th2 cytokine polymorphism and prognosis in patients with thoracic esophageal squamous cell cancer.

Materials and Methods

The study participants were 159 Japanese patients treated for thoracic esophageal squamous cell cancer with curative esophagectomy at Akita University Hospital. We determined the associations between prognosis following esophagectomy and genetic polymorphisms in Th1 cytokines (interleukin [IL]-2, Interferon-γ, IL-12β), and Th2 cytokines (IL-4, IL-10).

Results

IL-2 −330T>G genetic polymorphism was significantly associated with prognosis after esophagectomy. Univariate and multivariate analyses using a Cox proportional hazards model revealed that patients carrying the IL-2 −330G/G genotype had a significantly poorer prognosis than those carrying the T/G or T/T genotype. However, IL-2 −330T>G polymorphism was not associated with preoperative serum IL-2 levels. Moreover, interferon-γ, IL-12β, IL-4, and IL-10 genetic polymorphisms were not associated with prognosis after esophagectomy for thoracic esophageal squamous cell cancer.

Conclusions

It is suggested that IL-2 −330T>G genetic polymorphism may be a predictive factor for prognosis in patients receiving esophagectomy for thoracic esophageal squamous cell cancer.

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References

  1. Kranzfelder M, Büchler P, Lange K, Friess H. Treatment options for squamous cell cancer of the esophagus: a systematic review of the literature. J Am Coll Surg. 2010;210:351–9.

    Article  PubMed  Google Scholar 

  2. Penman ID, Henry E. Advanced esophageal cancer. Gastrointest Endosc Clin N Am. 2005;15:101–16.

    Article  PubMed  Google Scholar 

  3. Mariette C, Taillier G, Van Seuningen I, Triboulet JP. Factors affecting postoperative course and survival after en bloc resection for esophageal carcinoma. Ann Thorac Surg. 2004;78:1177–83.

    Article  PubMed  Google Scholar 

  4. Stocker G, Ott K, Henningsen N, Becker K, Hapfelmeier A, Lordick F, et al. CyclinD1 and interleukin-1 receptor antagonist polymorphisms are associated with prognosis in neoadjuvant-treated gastric carcinoma. Eur J Cancer. 2009;45:3326–35.

    Article  PubMed  CAS  Google Scholar 

  5. Lurje G, Zhang W, Schultheis AM, Yang D, Groshen S, Hendifar AE, et al. Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer. Ann Oncol. 2008;19:1734–41.

    Article  PubMed  CAS  Google Scholar 

  6. Schöndorf T, Eisele L, Göhring UJ, Valter MM, Warm M, Mallmann P, et al. The V109G polymorphism of the p27 gene CDKN1B indicates a worse outcome in node-negative breast cancer patients. Tumour Biol. 2004;25:306–12.

    Article  PubMed  Google Scholar 

  7. Liu G, Gurubhagavatula S, Zhou W, Wang Z, Yeap BY, Asomaning K, et al. Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib. Pharmacogenomics J. 2008;8:129–38.

    Article  PubMed  CAS  Google Scholar 

  8. Lagmay JP, London WB, Gross TG, Termuhlen A, Sullivan N, Axel A, et al. Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor). Clin Cancer Res. 2009;15:5234–9.

    Article  PubMed  CAS  Google Scholar 

  9. Okuno T, Tamura T, Yamamori M, Chayahara N, Yamada T, Miki I, et al. Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese. Am J Clin Oncol. 2007;30:252–7.

    Article  PubMed  CAS  Google Scholar 

  10. Sarbia M, Stahl M, von Weyhern C, Weirich G, Pühringer-Oppermann F. The prognostic significance of genetic polymorphisms (methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, thymidilate synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma. Br J Cancer. 2006;94:203–7.

    Article  PubMed  CAS  Google Scholar 

  11. Wu X, Gu J, Wu TT, Swisher SG, Liao Z, Correa AM, et al. Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol. 2006;24:3789–98.

    Article  PubMed  CAS  Google Scholar 

  12. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9:798–809.

    Article  PubMed  CAS  Google Scholar 

  13. Onoé K, Yanagawa Y, Minami K, Iijima N, Iwabuchi K. Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells. Immunol Res. 2007;38:319–32.

    Article  PubMed  Google Scholar 

  14. Ross OA, Curran MD, Meenagh A, Williams F, Barnett YA, Middleton D, et al. Study of age-association with cytokine gene polymorphisms in an aged Irish population. Mech Ageing Dev. 2003;124:199–206.

    Article  PubMed  CAS  Google Scholar 

  15. Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV. A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol. 2000;61:863–6.

    Article  PubMed  CAS  Google Scholar 

  16. Hall MA, McGlinn E, Coakley G, Fisher SA, Boki K, Middleton D, et al. Genetic polymorphism of IL-12 p40 gene in immune-mediated disease. Genes Immun. 2000;1:219–24.

    Article  PubMed  CAS  Google Scholar 

  17. Noguchi E, Shibasaki M, Arinami T, Takeda K, Yokouchi Y, Kawashima T, et al. Association of asthma and the interleukin-4 promoter gene in Japanese. Clin Exp Allergy. 1998;28:449–53.

    Article  PubMed  CAS  Google Scholar 

  18. Edwards-Smith CJ, Jonsson JR, Purdie DM, Bansal A, Shorthouse C, Powell EE. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa. Hepatology. 1999;30:526–30.

    Article  PubMed  CAS  Google Scholar 

  19. Hyngstrom JR, Posner MC. Neoadjuvant strategies for the treatment of locally advanced esophageal cancer. J Surg Oncol. 2010;101:299–304.

    Article  PubMed  CAS  Google Scholar 

  20. Udagawa H. Chemoradiotherapy: its effectiveness, toxicity, and perspective in the treatment of esophageal cancer. Ann Thorac Cardiovasc Surg. 2009;15:359–61.

    PubMed  Google Scholar 

  21. Lucey DR, Clerici M, Shearer GM. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev. 1996;9:532–62.

    PubMed  CAS  Google Scholar 

  22. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.

    Article  PubMed  CAS  Google Scholar 

  23. D’Souza WN, Lefrancois L. IL-2 is not required for the initiation of CD8 T cell cycling but sustains expansion. J Immunol. 2003;171:5727–35.

    PubMed  Google Scholar 

  24. Lenardo MJ. Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis. Nature. 1991;353:858–61.

    Article  PubMed  CAS  Google Scholar 

  25. John S, Turner D, Donn R, Sinnott P, Worthington J, Ollier WE, et al. Two novel biallelic polymorphisms in the IL-2 gene. Eur J Immunogenet. 1998;25:419–20.

    Article  PubMed  CAS  Google Scholar 

  26. Hoffmann SC, Stanley EM, Darrin Cox E, Craighead N, DiMercurio BS, Koziol DE, et al. Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation. 2001;72:1444–50.

    Article  PubMed  CAS  Google Scholar 

  27. Matesanz F, Fedetz M, Leyva L, Delgado C, Fernandez O, Alcina A. Effects of the multiple sclerosis associated −330 promoter polymorphism in IL2 allelic expression. J Neuroimmunol. 2004;148:212–7.

    Article  PubMed  CAS  Google Scholar 

  28. Nishimura T, Nakui M, Sato M, Iwakabe K, Kitamura H, Sekimoto M, et al. The critical role of Th1-dominant immunity in tumor immunology. Cancer Chemother Pharmacol. 2000;46:52–61.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Akita University Graduate School of Medicine, Akita, Japan

    Satoru Motoyama MD, PhD, Kiyotomi Maruyama MD, PhD, Shuetsu Usami MD, PhD, Kei Yoshino MD, Toshinobu Nakatsu MD, Hajime Saito MD, PhD, Yoshihiro Minamiya MD, PhD & Jun-ichi Ogawa MD, PhD

  2. Department of Pharmacy, Akita University Hospital, Akita, Japan

    Masatomo Miura PhD & Yudai Hinai

Authors
  1. Satoru Motoyama MD, PhD
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  2. Masatomo Miura PhD
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  3. Yudai Hinai
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  4. Kiyotomi Maruyama MD, PhD
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  5. Shuetsu Usami MD, PhD
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  6. Kei Yoshino MD
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  7. Toshinobu Nakatsu MD
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  8. Hajime Saito MD, PhD
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  9. Yoshihiro Minamiya MD, PhD
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  10. Jun-ichi Ogawa MD, PhD
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Corresponding author

Correspondence to Satoru Motoyama MD, PhD.

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Motoyama, S., Miura, M., Hinai, Y. et al. Interleukin-2 −330T>G Genetic Polymorphism Associates with Prognosis Following Surgery for Thoracic Esophageal Squamous Cell Cancer. Ann Surg Oncol 18, 1995–2002 (2011). https://doi.org/10.1245/s10434-011-1553-2

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  • DOI: https://doi.org/10.1245/s10434-011-1553-2

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