Variants of Interleukin-16 Associated with Gastric Cancer Risk

  • Zhang, Tao (Department of Gastrointestinal Surgery, the Centre Hospital of Wuhan) ;
  • Wang, Hui (Department of Gastrointestinal Surgery, the Centre Hospital of Wuhan)
  • Published : 2013.09.30


Aim: We conducted a case-control matched study to investigate the role of IL-16 gene polymorphisms, rs4072111, rs1131445, rs4778889 and rs11556218, in the risk of gastric cancer in a Chinese population, also performing subgroup analysis by subsites. Methods: To test the hypothesis of involvement, we analyzed the four SNPs of IL16 in 347 cancer patients and 368 controls. Demographic data and other information were collected using a newly designed questionnaire. Genotyping of IL16 (rs4072111, rs1131445, rs4778889 and rs11556218) was performed in a 384-well plate format on the MassARRAY(R) platform. Results: In our study, we found the gastric cancer patients were more likely to be male and have a family history of cancer (P<0.05). We found the rs4778889 CC and rs11556218 GG genotype was significantly associated with 1.97 and 1.84-fold increased risk of non-cardia gastric cancer, while we did not find significant association between the four IL-16 SNPs and cardia gastric cancer. Conclusions: In conclusion, our study indicated that IL-16 rs4778889 CC and rs11556218 GG genotypes are associated with an increased risk of non-cardia gastric cancer in a Chinese population. Our results offer insights into the influence of IL-16 on development of gastric cancer.


Interleukin-16;gastric cancer;polymorphisms;Chinese population


  1. Yonemoto N, Furuse J, Okusaka T, et al (2007). A multi-center retrospective analysis of survival benefits of chemotherapy for unresectable biliary tract cancer. Jpn J Clin Oncol, 37, 843-51.
  2. Baier M, Bannert N, Werner A, et al (1997). Molecular cloning, sequence, expression, and processing of the interleukin 16 precursor. Proc Natl Acad Sci U S A, 94, 5273-7.
  3. Batai K, Shah E, Murphy AB, et al (2012). Fine-mapping of IL16 gene and prostate cancer risk in African Americans. Cancer Epidemiol Biomarkers Prev, 21, 2059-68.
  4. Chung YC, Chang YF (2003). Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol, 83, 222-6.
  5. Drwinga HL, Toji LH, Kim CH, et al (1993). NIGMS human/ rodent somatic cell hybrid mapping panels 1 and 2. Genomics, 16, 311-4.
  6. Gao LB, Liang WB, Xue H, et al (2009b). Genetic polymorphism of interleukin-16 and risk of nasopharyngeal carcinoma. Clin Chim Acta, 409, 132-5.
  7. Graham DY, Adam E, Reddy GT, et al (1991). Seroepidemiology of Helicobacter pylori infection in India; comparison of developing and developing countries. Dig Dis Sci, 36, 1084-8.
  8. Gao LB, Rao L, Wang YY, et al (2009a). The association of interleukin-16 polymorphisms with IL-16 serum levels and risk of colorectal and gastric cancer. Carcinogenesis, 30, 295-9.
  9. Ghoshal UC, Tiwari S, Dhingra S, et al (2008). Frequency of Helicobacter pylori and CagA antibody in patients with gastric neoplasm and controls: the Indian enigma. Dig Dis Sci, 53, 1215-22.
  10. Ghoshal UC, Tripathi S, Ghoshal U (2007). The Indian enigma of frequent H. pylori infection but infrequent gastric cancer: is the magic key in Indian diet, host's genetic make up, or friendly bug? Am J Gastroenterol, 102, 2113-4.
  11. Gu XJ, Cui B, Zhao ZF, et al (2008). Association of the interleukin (IL)-16 gene polymorphisms with Graves' disease. Clin Immunol, 127, 298-302.
  12. Huang H, Zeng Z, Zhang L, et al (2013). The association of interleukin-16 gene polymorphisms with susceptibility of coronary artery disease. Clin Biochem, 46, 241-4.
  13. International Agency for Research on Cancer (2008). Globocan 2008: Stomach Cancer incidence, Mortality and Prevalence Worldwide in 2008. IARC.
  14. Kai H, Kitadai Y, Kodama M, et al (2005). Involvement of proinflammatory cytokines IL-1beta and IL-6 in progression of human gastric carcinoma. Anticancer Res, 25, 709-13.
  15. Liebrich M, Guo LH, Schluesener HJ, et al (2007). Expression of interleukin-16 by tumor-associated macrophages/activated microglia in high-grade astrocytic brain tumors. Arch Immunol Ther Exp (Warsz), 55, 41-7.
  16. Milke L, Schulz K, Weigert A, et al (2013). Depletion of tristetraprolin in breast cancer cells increases interleukin-16 expression and promotes tumor infiltration with monocytes/ macrophages. Carcinogenesis, 34, 850-7.
  17. Li S, Deng Y, Chen ZP, et al (2011). Genetic polymorphism of interleukin-16 influences susceptibility to HBV-related hepatocellular carcinoma in a Chinese population. Infect Genet Evol, 11, 2083-8.
  18. Mahindra A, Anderson KC (2012). Role of interleukin 16 in multiple myeloma pathogenesis: a potential novel therapeutic target? J Natl Cancer Inst, 104, 964-5.
  19. Mathy NL, Scheuer W, Lanzendorfer M, et al (2000). Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes. Immunology, 100, 63-9.
  20. Nakayama EE, Wasi C, Ajisawa A, et al (2000). A new polymorphism in the promoter region of the human interleukin-16 (IL-16) gene. Genes Immun, 1, 293-4.
  21. 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.
  22. Parsonnet J, Friedman GD, Orentreich N, et al (1997). Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut, 40, 297-301.
  23. 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.
  24. Schneider MR, Hoeflich A, Fischer JR, et al (2000). Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells. Cancer Lett, 151, 31-8.
  25. Xue H, Lin B, An J, et al (2012). Interleukin-10-819 promoter polymorphism in association with gastric cancer risk. BMC Cancer, 12, 102.
  26. Shanmugham LN, Petrarca C, Frydas S, et al (2006). IL-15 an immunoregulatory and anti-cancer cytokine. Recent advances. J Exp Clin Cancer Res, 25, 529-36.
  27. Thomas G, Jacobs KB, Yeager M, et al (2008). Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet, 40, 310-5.
  28. Wu J, Wang Y, Zhang Y, Li L (2011). Association between interleukin-16 polymorphisms and risk of coronary artery disease. DNA Cell Biol, 30, 305-8.
  29. Yellapa A, Bahr JM, Bitterman P, et al (2012). Association of interleukin 16 with the development of ovarian tumor and tumor-associated neoangiogenesis in laying hen model of spontaneous ovarian cancer. Int J Gynecol Cancer, 22, 199-207.
  30. Yuzhalin A (2011). The role of interleukin DNA polymorphisms in gastric cancer. Hum Immunol, 72, 1128-36.
  31. Zhang Y, Center DM, Wu DM, et al (1998). Processing and activation of pro-interleukin-16 by caspase-3. J Biol Chem, 273, 1144-9.

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