Advertisement

Tumor Biology

, Volume 35, Issue 2, pp 1575–1580 | Cite as

Analysis of the association of interleukin-17 gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population

  • Xukui Zhang
  • Luming Zheng
  • Yinggang Sun
  • Xiaoqiao ZhangEmail author
Research Article

Abstract

We aimed to explore the association between interleukin-17 (IL-17) polymorphisms, Helicobacter pylori infection, and subsites in gastric cancer risk in a Chinese population. We genotyped three promoter polymorphisms (rs2275913G>A, rs3748067C>T, and rs763780T>C) of IL-17 in a case–control study of 260 gastric cancer patients and 512 healthy controls. An unconditional multiple logistical regression model was used to calculate the effects of IL-17 gene polymorphisms on gastric cancer risk. The rs2275913 AA (adjusted OR = 1.69, 95 % CI = 1.15–2.49) and rs3748067 TT (adjusted OR = 1.73, 95 % CI = 1.03–2.94) genotypes were associated with an increased risk of gastric cancer. We observed a significant interaction among rs2275913G>A, rs3748067C>T, and H. pylori infection on the risk of gastric cancer (p for interaction of 0.036 and 0.048, respectively). H. pylori infection subjects carrying the rs2275913 AA (adjusted OR = 2.48, 95 % CI = 1.49–4.12) and rs3748067 TT (adjusted OR = 2.54, 95 % CI = 1.34–5.12) genotypes had a greatly increased risk of gastric cancer compared to negative H. pylori participants. Similarly, subjects carrying the rs2275913 AA (adjusted OR = 2.09, 95 % CI = 1.25–3.45) and rs3748067 TT (adjusted OR = 2.29, 95 % CI = 1.20–4.20) genotypes had a moderately increased risk of noncardia gastric cancer. A significant interaction was observed between the rs2275913G>A and rs3748067C>T genotype and subsites of gastric cancer (p for interaction of 0.044 and 0.008, respectively). The rs2275913G>A and rs763780T>C polymorphisms increase gastric cancer risk, and interact with H. pylori infection and subsites. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer.

Keywords

Interleukin-17 Polymorphism H. pylori infection Gastric cancer Risk 

Notes

Acknowledgments

We thank the staff from the Department of General Surgery of PLA Jinan General Hospital and patients who provides blood samples for us.

Conflicts of interest

None

References

  1. 1.
    International Agency for Research on Cancer. Globocan 2008: stomach cancer incidence, mortality and prevalence worldwide in 2008. IARC; 2008.Google Scholar
  2. 2.
    Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, et al. Recent patterns in gastric cancer: a global overview. Int J Cancer. 2009;125:666–73.PubMedCrossRefGoogle Scholar
  3. 3.
    Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62.PubMedGoogle Scholar
  4. 4.
    International Agency for Research on Cancer. IARC working group on the evaluation of carcinogenic risks to humans, schistosomes, liver flukes, Helicobacter pylori. IARC monographs on the evaluation of carcinogenic risks to humans, vol. 61. Lyon: International Agency for Research on Cancer; 1994. p. 1–241.Google Scholar
  5. 5.
    Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Hatakeyama M. Helicobacter pylori CagA-a bacterial intruder conspiring gastric carcinogenesis. Int J Cancer. 2006;119:1217–23.PubMedCrossRefGoogle Scholar
  7. 7.
    Rutitzky LI, Lopes da Rosa JR, Stadecker MJ. Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17. J Immunol. 2005;175:3920–6.PubMedGoogle Scholar
  8. 8.
    Luzza F, Parrello T, Monteleone G, Sebkova L, Romano M, Zarrilli R, et al. Upregulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa. J Immunol. 2000;165:5332–7.PubMedGoogle Scholar
  9. 9.
    Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. J Clin Immunol. 2008;28:44–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Arisawa T, Tahara T, Shiroeda H, Matsue Y, Minato T, Nomura T, et al. Genetic polymorphisms of IL17A and pri-microRNA-938, targeting IL17A 3′-UTR, influence susceptibility to gastric cancer. Hum Immunol. 2012;73(7):747–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Nordang GBN, Viken MK, Hollis-Moffatt JE, Merriman TR, Forre OT, Helgetveit K, et al. Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patients from Norway and New Zealand. Rheumatology. 2009;48:367–70.PubMedCrossRefGoogle Scholar
  12. 12.
    Wu X, Zeng Z, Chen B, Yu J, Xue L, Hao Y, et al. Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer. Int J Cancer. 2010;127:86–92.PubMedCrossRefGoogle Scholar
  13. 13.
    Chen J, Deng Y, Zhao J, Luo Z, Peng W, Yang J, et al. The polymorphism of IL-17 G-152A was associated with childhood asthma and bacterial colonization of the hypopharynx in bronchiolitis. J Clin Immunol. 2010;30:539–45.PubMedCrossRefGoogle Scholar
  14. 14.
    Lee DY, Hong SW, Chang YG, Lee WY, Lee B. Clinical significance of preoperative inflammatory parameters in gastric cancer patients. J Gastric Cancer. 2013;13:111–6.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Sepulveda AR. Helicobacter, inflammation, and gastric cancer. Curr Pathobiol Rep. 2013;1:9–18.PubMedCrossRefGoogle Scholar
  16. 16.
    Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Hu D, Hu G, Zhu J, Shen Y, Kang H, Hong S. Association between polymorphisms of the IL-23R gene and allergic rhinitis in a Chinese Han population. PLoS One. 2013;8:e63858.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Hejr S, Karimi MH, Yaghobi R, Kamali-Sarvestani E, Geramizadeh B, Roozbeh J. Association of IL-17, IL-21, and IL-23R gene polymorphisms with HBV infection in kidney transplant patients. Viral Immunol. 2013;26:201–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Kadkhodazadeh M, Baghani Z, Ebadian AR, Youssefi N, Mehdizadeh AR, Azimi N. IL-17 gene polymorphism is associated with chronic periodontitis and peri-implantitis in Iranian patients: a cross-sectional study. Immunol Invest. 2013;42:156–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Shibata T, Tahara T, Hirata I, Arisawa T. Genetic polymorphism of interleukin-17A and -17F genes in gastric carcinogenesis. Hum Immunol. 2009;70:547–51.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang B, Rong G, Wei H, Zhang M, Bi J, Ma L, et al. The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun. 2008;374:533–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Meng XY, Zhou CH, Ma J, Jiang C, Ji P. Expression of interleukin-17 and its clinical significance in gastric cancer patients. Med Oncol. 2012;29:3024–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Caruso R, Pallone F, Monteleone G. Emerging role of IL-23/IL-17 axis in H. pylori-associated pathology. World J Gastroenterol. 2007;13:5547–51.PubMedGoogle Scholar
  24. 24.
    Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. Genetic polymorphisms of molecules associated with inflammation and immune response in Japanese subjects with functional dyspepsia. Int J Mol Med. 2007;20:717–23.PubMedGoogle Scholar
  25. 25.
    Kim MA, Lee HS, Yang HK, Kim WH. Clinicopathologic and protein expression differences between cardia carcinoma and noncardia carcinoma of the stomach. Cancer. 2005;103:1439–46.PubMedCrossRefGoogle Scholar
  26. 26.
    Correa P. The biological model of gastric carcinogenesis. IARC Sci Publ. 2004;157:301–10.PubMedGoogle Scholar
  27. 27.
    El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, et al. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology. 2003;124:1193–201.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Xukui Zhang
    • 1
  • Luming Zheng
    • 1
  • Yinggang Sun
    • 1
  • Xiaoqiao Zhang
    • 1
    Email author
  1. 1.Department of General SurgeryPLA Jinan General HospitalJinanChina

Personalised recommendations