Interleukin-10 Gene Promoter Polymorphisms and Risk of Gastric Cancer in a Chinese Population: Single Nucleotide and Haplotype Analyses

  • Pan, Xiong-Fei (Department of Epidemiology, West China School of Public Health, Sichuan University) ;
  • Yang, Shu-Juan (Department of Child and Adolescent Health, West China School of Public Health, Sichuan University) ;
  • Loh, Marie (Cancer Science Institute of Singapore, National University of Singapore) ;
  • Xie, Yao (Department of Epidemiology, West China School of Public Health, Sichuan University) ;
  • Wen, Yuan-Yuan (Department of Epidemiology, West China School of Public Health, Sichuan University) ;
  • Tian, Zhi (Department of Epidemiology, West China School of Public Health, Sichuan University) ;
  • Huang, He (Department of Epidemiology, West China School of Public Health, Sichuan University) ;
  • Lan, Hui (Department of Epidemiology, West China School of Public Health, Sichuan University) ;
  • Chen, Feng (Department of Epidemiology, West China School of Public Health, Sichuan University) ;
  • Soong, Richie (Cancer Science Institute of Singapore, National University of Singapore) ;
  • Yang, Chun-Xia (Department of Epidemiology, West China School of Public Health, Sichuan University)
  • Published : 2013.04.30


Objectives: Interleukin (IL) -10 is a potent cytokine with a dual ability to immunosuppress or immunostimulate. We aimed to explore the association of IL10 promoter polymorphisms with risk of gastric cancer (GC) in a Han population in Southwestern China. Methods: We enrolled 308 pairs of GC and control subjects from four hospitals and a community between October 2010 and August 2011 in a 1:1 matched case-control design. Demographic information was collected using a designed questionnaire. IL10-592 A>C and IL10-1082 A>G polymorphisms were determined by Sequenom MassARRAY analysis. Results: Patients with GC reported statistically higher proportions of family history of cancer (29.9% versus 10.7%, P<0.01) and alcohol drinking (54.6% versus 43.2%, P<0.01) than did controls. Similar results were observed in comparison between non-cardia GC patients and controls (P<0.01 and P=0.03). Variant genotypes of IL10-592 A>C and IL10-1082 A>G were not associated with overall GC risk (adjusted OR, 0.94, 95% CI, 0.66-1.33; adjusted OR, 1.00, 95% CI, 0.62-1.60). Sub-analysis showed that the IL10-592 AC/CC variant genotype was associated with decreased non-cardia GC risk (adjusted OR, 0.58; 95% CI, 0.36-0.95). No association was found between any of the IL10 haplotypes established from two polymorphisms and risk of non-cardia GC. Conclusions: In conclusion, our data do not link the two SNPs of IL10-592 and IL10-1082 with overall GC risk. We demonstrate that IL10-592 polymorphism is associated with protective effect against non-cardia GC. Our findings may offer insight into risk associated with the development of GC in this region.


Supported by : National Medical Research Council of Singapore


  1. Akdis M, Burgler S, Crameri R, et al (2011). Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases. J Allergy Clin Immunol, 127, 701-21 e1-70.
  2. Alpizar-Alpizar W, Perez-Perez GI, Une C, et al (2005). Association of interleukin-1B and interleukin-1RN polymorphisms with gastric cancer in a high-risk population of Costa Rica. Clin Exp Med, 5, 169-76.
  3. Bai XL, Sun LP, Liu J, et al (2008). Correlation of interleukin-10-1082G/a single nucleotide polymorphism to the risk of gastric cancer in north China: a case-control study [in Chinese]. Chin J Cancer, 27, 35-40.
  4. Bertuccio P, Chatenoud L, Levi F, et al (2009). Recent patterns in gastric cancer: a global overview. Int J Cancer, 125, 666-73.
  5. Blaser MJ (1999). Hypothesis: the changing relationships of Helicobacter pylori and humans: implications for health and disease. J Infect Dis, 179, 1523-30.
  6. Brown LM, Devesa SS (2002). Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am, 11, 235-56.
  7. Con SA, Takeuchi H, Con-Chin GR, et al (2009). Role of bacterial and genetic factors in gastric cancer in Costa Rica. World J Gastroenterol, 15, 211-8.
  8. Crawley E, Kay R, Sillibourne J, et al (1999). Polymorphic haplotypes of the interleukin-10 5' flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum, 42, 1101-8.<1101::AID-ANR6>3.0.CO;2-Y
  9. Crew KD, Neugut AI (2006). Epidemiology of gastric cancer. World J Gastroenterol, 12, 354-62.
  10. El-Omar EM, Rabkin CS, Gammon MD, et al (2003). Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology, 124, 1193-201.
  11. Ferlay J, Shin HR, Bray F, et al GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet], Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan., accessed on 25/2/2013.
  12. Gibson AW, Edberg JC, Wu J, et al (2001). Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol, 166, 3915-22.
  13. Guo W, Wang N, Wang YM, et al (2005). Interleukin-10-1082 promoter polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high-incidence region of north China. World J Gastroenterol, 11, 858-62.
  14. Jemal A, Center MM, Desantis C, Ward EM (2010). Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev, 19, 1893-907.
  15. Justenhoven C, Hamann U, Pesch B, et al (2004). ERCC2 genotypes and a corresponding haplotype are linked with breast cancer risk in a German population. Cancer Epidem Biomar, 13, 2059-64.
  16. Kamangar F, Dores GM, Anderson WF (2006). Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol, 24, 2137-50.
  17. Li Z, Zhang Z, He Z, et al (2009). A partition-ligationcombination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis ( Cell Res, 19, 519-23.
  18. Liu J, Song B, Wang JL, et al (2011). Polymorphisms of interleukin-10 promoter are not associated with prognosis of advanced gastric cancer. World J Gastroenterol, 17, 1362-7.
  19. Loh M, Koh KX, Yeo BH, et al (2009). Meta-analysis of genetic polymorphisms and gastric cancer risk: variability in associations according to race. Eur J Cancer, 45, 2562-8.
  20. Lu W, Pan K, Zhang L, et al (2005). Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor {alpha} and risk of gastric cancer in a Chinese population. Carcinogenesis, 26, 631-6.
  21. Mccoll KE, El-Omar E, Gillen D (2000). Helicobacter pylori gastritis and gastric physiology. Gastroenterol Clin North Am, 29, 687-703, viii.
  22. Mocellin S, Marincola FM, Young HA (2005). Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol, 78, 1043-51.
  23. Ni P, Xu H, Xue H, et al (2012). A meta-analysis of interleukin-10-1082 promoter polymorphism associated with gastric cancer risk. DNA Cell Biol, 31, 582-91.
  24. Niven DJ, Berthiaume LR, Fick GH, Laupland KB (2012). Matched case-control studies: a review of reported statistical methodology. Clin Epidemiol, 4, 99-110.
  25. Rad R, Dossumbekova A, Neu B, et al (2004). Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection. Gut, 53, 1082-9.
  26. Salazar-Onfray F, Lopez MN, Mendoza-Naranjo A (2007). Paradoxical effects of cytokines in tumor immune surveillance and tumor immune escape. Cytokine Growth Factor Rev, 18, 171-82.
  27. Seno H, Satoh K, Tsuji S, et al (2007). Novel interleukin-4 and interleukin-1 receptor antagonist gene variations associated with non-cardia gastric cancer in Japan: Comprehensive analysis of 207 polymorphisms of 11 cytokine genes. J Gastroenterol Hepatol, 22, 729-37.
  28. Shi YY, He L (2005). SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res, 15, 97-8.
  29. Shin CM, Kim N, Lee HS, et al (2011). Intrafamilial aggregation of gastric cancer: a comprehensive approach including environmental factors, Helicobacter pylori virulence, and genetic susceptibility. Eur J Gastroenterol Hepatol, 23, 411-7.
  30. Sicinschi LA, Lopez-Carrillo L, Camargo MC, et al (2006). Gastric cancer risk in a Mexican population: role of Helicobacter pylori CagA positive infection and polymorphisms in interleukin-1 and-10 genes. Int J Cancer, 118, 649-57.
  31. Turner DM, Williams DM, Sankaran D, et al (1997). An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet, 24, 1-8.
  32. Wang J, Ding Q, Shi Y, et al (2012). The interleukin-10-1082 promoter polymorphism and cancer risk: a meta-analysis. Mutagenesis, 27, 305-12.
  33. Wen YY, Pan XF, Loh M, et al (2012). ADPRT Val762Ala and XRCC1 Arg194Trp polymorphisms and risk of gastric cancer in Sichuan of China. Asian Pac J Cancer Prev, 13, 2139-44.
  34. Won HH, Kim JW, Kim MJ, et al (2010). Interleukin 10 polymorphisms differentially influence the risk of gastric cancer in East Asians and Caucasians. Cytokine, 51, 73-7.
  35. Wu MS, Wu CY, Chen CJ, et al (2003). Interleukin-10 genotypes associate with the risk of gastric carcinoma in Taiwanese Chinese. Int J Cancer, 104, 617-23.
  36. Yuzhalin A (2011). The role of interleukin DNA polymorphisms in gastric cancer. Hum Immunol, 72, 1128-36.
  37. Zambon CF, Basso D, Navaglia F, et al (2005). Pro-and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome. Cytokine, 29, 141-52.
  38. Zhou Y, Hu W, Zhuang W, Wu X (2011). Interleukin-10-1082 promoter polymorphism and gastric cancer risk in a Chinese Han population. Mol Cell Biochem, 347, 89-93.
  39. Zhuang W, Wu XT, Zhou Y, et al (2010). Interleukin10-592 promoter polymorphism associated with gastric cancer among Asians: a meta-analysis of epidemiologic studies. Dig Dis Sci, 55, 1525-32.

Cited by

  1. Association Analysis of Common Genetic Variations in MUC5AC Gene with the Risk of Non-cardia Gastric Cancer in a Chinese Population vol.15, pp.10, 2014,
  2. Combined Effects of Six Cytokine Gene Polymorphisms and SNP-SNP Interactions on Hepatocellular Carcinoma Risk in Southern Guangxi, China vol.15, pp.16, 2014,
  3. Association of Cytokine Gene Polymorphisms with Gastritis in a Kazakh Population vol.15, pp.18, 2014,
  4. Interleukin-4 and -8 Gene Polymorphisms and Risk of Gastric Cancer in a Population in Southwestern China vol.15, pp.7, 2014,
  5. Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases vol.32, pp.8, 2015,
  6. The -1082A>G polymorphism in promoter region of interleukin-10 and risk of digestive cancer: a meta-analysis vol.4, pp.1, 2015,
  7. Interleukin-16 polymorphisms as new promising biomarkers for risk of gastric cancer vol.37, pp.2, 2016,