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.


  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. 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.
  8. 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.
  9. 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.
  10. 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.
  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. 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.
  17. 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.
  18. 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.
  19. 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.
  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. 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.
  26. 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.
  27. 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.
  28. Xue H, Lin B, An J, et al (2012). Interleukin-10-819 promoter polymorphism in association with gastric cancer risk. BMC Cancer, 12, 102.
  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.

Cited by

  1. Interleukin-12 and Interleukin-6 Gene Polymorphisms and Risk of Bladder Cancer in the Iranian Population vol.15, pp.18, 2014,
  2. Genetic Polymorphisms of Interleukin-16 and Risk of Knee Osteoarthritis vol.10, pp.5, 2015,
  3. Interleukin-16 polymorphisms as new promising biomarkers for risk of gastric cancer vol.37, pp.2, 2016,
  4. Association of genetic polymorphisms of interleukins with gastric cancer and precancerous gastric lesions in a high-risk Chinese population vol.37, pp.2, 2016,
  5. Association of interleukin-16 polymorphisms with disease progression and susceptibility in endometriosis vol.43, pp.5, 2016,
  6. The expression of IGF-1R in Helicobacter pylori-infected intestinal metaplasia and gastric cancer vol.59, pp.1, 2016,
  7. Interleukin-16 Polymorphism Is Associated with an Increased Risk of Glioma vol.18, pp.10, 2014,
  8. Diagnostic and prognostic value of serum interleukin-16 in patients with gastric cancer vol.16, pp.6, 2017,