Tumor Biology

, Volume 35, Issue 3, pp 2675–2679 | Cite as

Association between IL-4 -589C>T polymorphism and colorectal cancer risk

  • Qiang Li
  • Qian Wang
  • Xiaoyan Xu
  • Songtao Ren
  • Li Wang
Research Article


In order to make a comprehensive assessment of the potential association between interleukin-4 (IL-4) -589C>T and colorectal cancer (CRC) susceptibility, we conducted a meta-analysis of six epidemiological studies, which included 1,317 CRC patients and 1,659 controls. The data showed that IL-4 -589C>T was not associated with increased CRC risk in the overall population. In the subgroup analysis of IL-4 -589C>T, the results did not change when the analyses were restricted to race. Based on this meta-analysis, we conclude that IL-4 -589C>T may be not a risk factor for CRC development. Further research is needed to assess possible gene–gene or gene–environment–lifestyle interactions on CRC.


Colorectal cancer Interleukin-4 Meta-analysis Risk 


Conflicts of interest



  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Lin YW, Wang JL, Chen HM, Zhang YJ, Lu R, Ren LL, et al. Folic acid supplementary reduce the incidence of adenocarcinoma in a mouse model of colorectal cancer: microarray gene expression profile. J Exp Clin Cancer Res. 2011;30:116.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Kemp RA, Black MA, McCall J, Yoon HS, Phillips V, Anjomshoaa A, et al. T cell subpopulations in lymph nodes may not be predictive of patient outcome in colorectal cancer. J Exp Clin Cancer Res. 2011;30:78.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Ritchie SA, Jayasinghe D, Davies GF, Ahiahonu P, Ma H, Goodenowe DB. Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity. J Exp Clin Cancer Res. 2011;30:59.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Hutter CM, Chang-Claude J, Slattery ML, Pflugeisen BM, Lin Y, Duggan D, et al. Characterization of gene–environment interactions for colorectal cancer susceptibility loci. Cancer Res. 2012;72(8):2036–44.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Zhong R, Liu L, Zou L, Sheng W, Zhu B, Xiang H, et al. Genetic variations in the TGFβ signaling pathway, smoking and risk of colorectal cancer in a Chinese population. Carcinogenesis. 2013;34(4):936–42.PubMedCrossRefGoogle Scholar
  7. 7.
    Baniyash M. Chronic inflammation, immunosuppression and cancer: new insights and outlook. Semin Cancer Biol. 2006;16:80–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Zhang H, Xu Y, Zhang Z, Liu R, Ma B. Association between COX-2 rs2745557 polymorphism and prostate cancer risk: a systematic review and meta-analysis. BMC Immunol. 2012;13:14.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Lakatos PL, Lakatos L. Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J Gastroenterol. 2008;14:3937–47.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Triantafillidis JK, Nasioulas G, Kosmidis PA. Colorectal cancer and inflammatory bowel disease: epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies. Anticancer Res. 2009;29:2727–37.PubMedGoogle Scholar
  11. 11.
    Kelso A. Cytokines: principles and prospects. Immunol Cell Biol. 1998;76:300.PubMedCrossRefGoogle Scholar
  12. 12.
    Noguchi E, Nukaga-Nishio Y, Jian Z, Yokouchi Y, Kamioka M, et al. Haplotypes of the 5′ region of the IL-4 gene and SNPs in the intergene sequence between the IL-4 and IL-13 genes are associated with atopic asthma. Hum Immunol. 2001;62:1251–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Suchy J, Kłujszo-Grabowska E, Kładny J, Cybulski C, Wokołorczyk D, Szymańska-Pasternak J, et al. Inflammatory response gene polymorphisms and their relationship with colorectal cancer risk. BMC Cancer. 2008;8:112.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Wilkening S, Tavelin B, Canzian F, Enquist K, Palmqvist R, Altieri A, et al. Interleukin promoter polymorphisms and prognosis in colorectal cancer. Carcinogenesis. 2008;29:1202–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Yannopoulos A, Nikiteas N, Chatzitheofylaktou A, Tsigris C. The (−590 C/T) polymorphism in the interleukin-4 gene is associated with increased risk for early stages of corolectal adenocarcinoma. In Vivo. 2007;21:1031–5.PubMedGoogle Scholar
  16. 16.
    Cozar JM, Romero JM, Aptsiauri N, Vazquez F, Vilchez JR, Tallada M, et al. High incidence of CTLA-4 AA (CT60) polymorphism in renal cell cancer. Hum Immunol. 2007;68:698–704.PubMedCrossRefGoogle Scholar
  17. 17.
    Landi S, Bottari F, Gemignani F, Gioia-Patricola L, Guino E, Osorio A, et al. Interleukin-4 and interleukin-4 receptor polymorphisms and colorectal cancer risk. Eur J Cancer. 2007;43:762–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Gunter MJ, Canzian F, Landi S, Chanock SJ, Sinha R, Rothman N. Inflammation-related gene polymorphisms and colorectal adenoma. Cancer Epidemiol Biomarkers Prev. 2006;15:1126–31.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang H, Qi C, Li L, Luo F, Xu Y. Clinical significance of NUCB2 mRNA expression in prostate cancer. J Exp Clin Cancer Res. 2013;32:56.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Zhang H, Qi C, Wang A, Li L, Xu Y. High expression of nucleobindin 2 mRNA: an independent prognostic factor for overall survival of patients with prostate cancer. Tumor Biol. 2013. doi: 10.1007/s13277-013-1268-z.Google Scholar
  21. 21.
    Zhang H, Qi C, Wang A, Yao B, Li L, Wang Y, et al. Prognostication of prostate cancer based on NUCB2 protein assessment: NUCB2 in prostate cancer. J Exp Clin Cancer Res. 2013;32:77.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Zhang H, Ma H, Xu Y, Li L. Association of SMAD7 rs12953717 polymorphism with cancer: a meta-analysis. PLoS ONE. 2013;8:e58170.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Zhang H, Ma H, Li L, Zhang Z, Xu Y. Association of methylenetetrahydrofolate dehydrogenase 1 polymorphisms with cancer: a meta-analysis. PLoS One. 2013;8:e69366.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Zhang H, Li L, Xu Y. CYP1B1 polymorphisms and susceptibility to prostate cancer: a meta-analysis. PLoS One. 2013;8:e68634.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Abaza MS, Bahman AM, Al-Attiyah RJ, Kollamparambil AM. Synergistic induction of apoptosis and chemosensitization of human colorectal cancer cells by histone deacetylase inhibitor, scriptaid, and proteasome inhibitors: potential mechanisms of action. Tumor Biol. 2012;33(6):1951–72.CrossRefGoogle Scholar
  26. 26.
    Bordignon V, Cordiali-Fei P, Rinaldi M, Signori E, Cottarelli A, Zonfrillo M, et al. Evaluation of antigen specific recognition and cell mediated cytotoxicity by a modified lysispot assay in a rat colon carcinoma model. J Exp Clin Cancer Res. 2012;31:9.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Rajkumar VS, Boxer G, Robson M, Muddle J, Papastavrou Y, Pedley RB. A comparative study of PDGFR inhibition with imatinib on radiolabeled antibody targeting and clearance in two pathologically distinct models of colon adenocarcinoma. Tumor Biol. 2012;33(6):2019–29.CrossRefGoogle Scholar
  28. 28.
    Petraki C, Youssef YM, Dubinski W, Lichner Z, Scorilas A, Pasic MD, et al. Evaluation and prognostic significance of human tissue kallikrein-related peptidase 10 (KLK10) in colorectal cancer. Tumor Biol. 2012;33(4):1209–14.CrossRefGoogle Scholar
  29. 29.
    Findeisen P, Costina V, Yepes D, Hofheinz R, Neumaier M. Functional protease profiling with reporter peptides in serum specimens of colorectal cancer patients: demonstration of its routine diagnostic applicability. J Exp Clin Cancer Res. 2012;31:56.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Song M, Zang W, Zhang B, Cao J, Yang G. GCS overexpression is associated with multidrug resistance of human HCT-8 colon cancer cells. J Exp Clin Cancer Res. 2012;31:23.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Pérez-Ruiz E, Rueda A, Pereda T, Alcaide J, Bautista D, Rivas-Ruiz F, et al. Involvement of K-RAS mutations and amino acid substitutions in the survival of metastatic colorectal cancer patients. Tumor Biol. 2012;33(6):1829–35.CrossRefGoogle Scholar
  32. 32.
    Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81.PubMedCrossRefGoogle Scholar
  33. 33.
    Jancik S, Drabek J, Berkovcova J, Xu YZ, Stankova M, Klein J, et al. A comparison of direct sequencing, pyrosequencing, high resolution melting analysis, TheraScreen DxS, and the K-ras StripAssay for detecting KRAS mutations in non small cell lung carcinomas. J Exp Clin Cancer Res. 2012;31:79.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Sung JJ, Lau JY, Goh KL, Leung WK, Asia PacificWorking Group on Colorectal Cancer. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol. 2005;6:871–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Coco C, Zannoni GF, Caredda E, Sioletic S, Boninsegna A, Migaldi M, et al. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients. J Exp Clin Cancer Res. 2012;31:71.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Cleary SP, Cotterchio M, Shi E, Gallinger S, Harper P. Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk. Am J Epidemiol. 2010;172:1000–14.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Qiang Li
    • 1
  • Qian Wang
    • 2
  • Xiaoyan Xu
    • 3
  • Songtao Ren
    • 4
  • Li Wang
    • 5
  1. 1.Proctology DepartmentLiaocheng People’s HospitalLiaocheng CityChina
  2. 2.Ultrasonography DepartmentLiaocheng People’s HospitalLiaocheng CityChina
  3. 3.Neurology DepartmentLiaocheng People’s HospitalLiaocheng CityChina
  4. 4.Department of NeurosurgeryLiaocheng People’s HospitalLiaocheng CityChina
  5. 5.Department of Gynaecology and ObstetricsLiaocheng People’s HospitalLiaocheng CityChina

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