Skip to main content

Advertisement

SpringerLink
Log in

The polymorphisms of IL-4, IL-4R and IL-13 genes and bladder cancer risk in a Chinese population: a case–control study

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Accumulating evidence suggests that inflammatory process may play a role in bladder carcinogenesis. However, the exact mechanisms of how the inflammatory factors associate with bladder cancer risk are still unknown. In this study, we explored whether polymorphisms (i.e. IL-4 C-590T, IL-4R Ile50Val, IL-4R Ser478Pro, IL-4R Gln551Arg, IL-13 C-1055T and IL-13 Arg130Gln) of IL-4, IL-4R and IL-13 genes predicted Chinese bladder cancer risk in 817 bladder cancer and 1,141 controls. Genotyping was performed by using the TaqMan method. We did not find any overall association between these single nucleotide polymorphisms (SNPs) and bladder cancer susceptibility in a Chinese population. However, in the classification and regression tree (CART) analysis, we found that carriers of IL-13 C-1055T variant genotype in smokers had a 2.57-fold increased bladder cancer risk with a 55% patient rate (OR = 2.57; 95% CI = 1.93-3.43), comparing with non-smokers. Similar result was also observed in combination of IL-13 C-1055T and IL-13 Arg130Gln in smokers. By multifactor dimensionality reduction (MDR) analysis, the best interaction model was the two-factor model that smokers with the IL-13 C-1055T genotypes were the subgroup to predict bladder cancer risk. The results suggested that the genetic variants in IL-4, IL-4R and IL-13 genes might modulate the bladder cancer risk in a Chinese population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kakehi Y, Hirao Y, Kim WJ, Ozono S, Masumori N, Miyanaga N, Nasu Y, Yokomizo A (2010) Bladder Cancer Working Group report. Jpn J Clin Oncol 40(Suppl 1):i57–i64

    Article  PubMed  Google Scholar 

  2. Parkin DM (2004) International variation. Oncogene 23(38):6329–6340

    Article  PubMed  CAS  Google Scholar 

  3. Hainaut P, Pfeifer GP (2001) Patterns of p53 G→T transversions in lung cancers reflect the primary mutagenic signature of DNA-damage by tobacco smoke. Carcinogenesis 22(3):367–374

    Article  PubMed  CAS  Google Scholar 

  4. Ames BN, Gold LS, Willett WC (1995) The causes and prevention of cancer. Proc Natl Acad Sci USA 92(12):5258–5265

    Article  PubMed  CAS  Google Scholar 

  5. Opal SM, DePalo VA (2000) Anti-inflammatory cytokines. Chest 117(4):1162–1172

    Article  PubMed  CAS  Google Scholar 

  6. Noguchi E, Nukaga-Nishio Y, Jian Z, Yokouchi Y, Kamioka M, Yamakawa-Kobayashi K, Hamaguchi H, Matsui A, Shibasaki M, Arinami T (2001) 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 62(11):1251–1257

    Article  PubMed  CAS  Google Scholar 

  7. Mitsuyasu H, Izuhara K, Mao XQ, Gao PS, Arinobu Y, Enomoto T, Kawai M, Sasaki S, Dake Y, Hamasaki N, Shirakawa T, Hopkin JM (1998) Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma. Nat Genet 19(2):119–120

    Article  PubMed  CAS  Google Scholar 

  8. Kruse S, Japha T, Tedner M, Sparholt SH, Forster J, Kuehr J, Deichmann KA (1999) The polymorphisms S503P and Q576R in the interleukin-4 receptor alpha gene are associated with atopy and influence the signal transduction. Immunology 96(3):365–371

    Article  PubMed  CAS  Google Scholar 

  9. Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA (1997) The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med 337(24):1720–1725

    Article  PubMed  CAS  Google Scholar 

  10. Palmer LJ, Daniels SE, Rye PJ, Gibson NA, Tay GK, Cookson WO, Goldblatt J, Burton PR, LeSouef PN (1998) Linkage of chromosome 5q and 11q gene markers to asthma-associated quantitative traits in Australian children. Am J Respir Crit Care Med 158(6):1825–1830

    PubMed  CAS  Google Scholar 

  11. Callard RE, Matthews DJ, Hibbert L (1996) IL-4 and IL-13 receptors: are they one and the same? Immunol Today 17(3):108–110

    Article  PubMed  CAS  Google Scholar 

  12. Terabe M, Matsui S, Noben-Trauth N, Chen H, Watson C, Donaldson DD, Carbone DP, Paul WE, Berzofsky JA (2000) NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 1(6):515–520

    Article  PubMed  CAS  Google Scholar 

  13. Cameron L, Webster RB, Strempel JM, Kiesler P, Kabesch M, Ramachandran H, Yu L, Stern DA, Graves PE, Lohman IC, Wright AL, Halonen M, Klimecki WT, Vercelli D (2006) Th2 cell-selective enhancement of human IL13 transcription by IL13-1112C>T, a polymorphism associated with allergic inflammation. J Immunol 177(12):8633–8642

    PubMed  CAS  Google Scholar 

  14. Graves PE, Kabesch M, Halonen M, Holberg CJ, Baldini M, Fritzsch C, Weiland SK, Erickson RP, von Mutius E, Martinez FD (2000) A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children. J Allergy Clin Immunol 105(3):506–513

    Article  PubMed  CAS  Google Scholar 

  15. Wang M, Wang M, Yuan L, Wu D, Zhang Z, Yin C, Fu G, Wei Q, Zhang Z (2010) A novel XPF -357A>C polymorphism predicts risk and recurrence of bladder cancer. Oncogene 29(13):1920–1928

    Article  PubMed  CAS  Google Scholar 

  16. Hochberg Y, Benjamini Y (1990) More powerful procedures for multiple significance testing. Stat Med 9(7):811–818

    Article  PubMed  CAS  Google Scholar 

  17. Zhang H, Bonney G (2000) Use of classification trees for association studies. Genet Epidemiol 19(4):323–332

    Article  PubMed  CAS  Google Scholar 

  18. Hahn LW, Ritchie MD, Moore JH (2003) Multifactor dimensionality reduction software for detecting gene–gene and gene–environment interactions. Bioinformatics 19(3):376–382

    Article  PubMed  CAS  Google Scholar 

  19. Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH (2001) Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 69(1):138–147

    Article  PubMed  CAS  Google Scholar 

  20. Lin WW, Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117(5):1175–1183

    Article  PubMed  CAS  Google Scholar 

  21. Terabe M, Matsui S, Park JM, Mamura M, Noben-Trauth N, Donaldson DD, Chen W, Wahl SM, Ledbetter S, Pratt B, Letterio JJ, Paul WE, Berzofsky JA (2003) Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J Exp Med 198(11):1741–1752

    Article  PubMed  CAS  Google Scholar 

  22. Nedoszytko B, Niedoszytko M, Lange M, van Doormaal J, Glen J, Zablotna M, Renke J, Vales A, Buljubasic F, Jassem E, Roszkiewicz J, Valent P (2009) Interleukin-13 promoter gene polymorphism -1112C/T is associated with the systemic form of mastocytosis. Allergy 64(2):287–294

    Article  PubMed  CAS  Google Scholar 

  23. Wang SS, Carreon JD, Hanchard B, Chanock S, Hisada M (2009) Common genetic variants and risk for non-Hodgkin lymphoma and adult T-cell lymphoma/leukemia in Jamaica. Int J Cancer 125(6):1479–1482

    Article  PubMed  CAS  Google Scholar 

  24. MalekZadeh K, Nikbakht M, Sadeghi IA, Singh SK, Sobti RC (2010) Overexpression of IL-13 in patients with bladder cancer. Cancer Invest 28(2):201–207

    Article  PubMed  CAS  Google Scholar 

  25. Sameni S, Ghayumi MA, Mortazavi G, Faghih Z, Kashef MA, Ghaderi A (2009) Lack of association between interleukin-13 gene polymorphisms (-1055 C/T and +2044 G/A) in Iranian patients with lung cancer. Mol Biol Rep 36(5):1001–1005

    Article  PubMed  CAS  Google Scholar 

  26. Muller-Hermelink N, Braumuller H, Pichler B, Wieder T, Mailhammer R, Schaak K, Ghoreschi K, Yazdi A, Haubner R, Sander CA, Mocikat R, Schwaiger M, Forster I, Huss R, Weber WA, Kneilling M, Rocken M (2008) TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell 13(6):507–518

    Article  PubMed  Google Scholar 

  27. Swain SL, Weinberg AD, English M, Huston G (1990) IL-4 directs the development of Th2-like helper effectors. J Immunol 145(11):3796–3806

    PubMed  CAS  Google Scholar 

  28. Olson SH, Orlow I, Simon J, Tommasi D, Roy P, Bayuga S, Ludwig E, Zauber AG, Kurtz RC (2007) Allergies, variants in IL-4 and IL-4R alpha genes, and risk of pancreatic cancer. Cancer Detect Prev 31(5):345–351

    Article  PubMed  CAS  Google Scholar 

  29. Sugimoto M, Yamaoka Y, Furuta T (2010) Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer. World J Gastroenterol 16(10):1188–1200

    Article  PubMed  CAS  Google Scholar 

  30. Landi S, Bottari F, Gemignani F, Gioia-Patricola L, Guino E, Osorio A, de Oca J, Capella G, Canzian F, Moreno V (2007) Interleukin-4 and interleukin-4 receptor polymorphisms and colorectal cancer risk. Eur J Cancer 43(4):762–768

    Article  PubMed  CAS  Google Scholar 

  31. Chen M, Kamat AM, Huang M, Grossman HB, Dinney CP, Lerner SP, Wu X, Gu J (2007) High-order interactions among genetic polymorphisms in nucleotide excision repair pathway genes and smoking in modulating bladder cancer risk. Carcinogenesis 28(10):2160–2165

    Article  PubMed  CAS  Google Scholar 

  32. Cozen W, Diaz-Sanchez D, James Gauderman W, Zadnick J, Cockburn MG, Gill PS, Masood R, Hamilton AS, Jyrala M, Mack TM (2004) Th1 and Th2 cytokines and IgE levels in identical twins with varying levels of cigarette consumption. J Clin Immunol 24(6):617–622

    Article  PubMed  CAS  Google Scholar 

  33. Simhan HN, Caritis SN, Hillier SL, Krohn MA (2005) Cervical anti-inflammatory cytokine concentrations among first-trimester pregnant smokers. Am J Obstet Gynecol 193(6):1999–2003

    Article  PubMed  CAS  Google Scholar 

  34. Schmid-Grendelmeier P, Altznauer F, Fischer B, Bizer C, Straumann A, Menz G, Blaser K, Wuthrich B, Simon HU (2002) Eosinophils express functional IL-13 in eosinophilic inflammatory diseases. J Immunol 169(2):1021–1027

    PubMed  CAS  Google Scholar 

  35. Margel D, Pevsner-Fischer M, Baniel J, Yossepowitch O, Cohen IR (2011) Stress proteins and cytokines are urinary biomarkers for diagnosis and staging of bladder cancer. Eur Urol 59(1):113–119

    Article  PubMed  CAS  Google Scholar 

  36. Zhai R, Chen F, Liu G, Su L, Kulke MH, Asomaning K, Lin X, Heist RS, Nishioka NS, Sheu CC, Wain JC, Christiani DC (2010) Interactions among genetic variants in apoptosis pathway genes, reflux symptoms, body mass index, and smoking indicate two distinct etiologic patterns of esophageal adenocarcinoma. J Clin Oncol 28(14):2445–2451

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partly supported by National Natural Science Foundation of China (30872084, 30972444, 30901166, and 81102089), the key program of National Natural Science Foundation of Jiangsu Province (BK2010080), National Natural Science Foundation of Jiangsu Province (BK2011773), The Key Program for Basic Research of Jiangsu Provincial Department of Education (08KJA330001, and 11KJB330002), and the Project Funded by the Priority Academic Program Development of Jiangsu (Public Health and Preventive Medicine).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Molecular & Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 210029, China

    Haiyan Chu, Lan Ma, Meilin Wang, Danni Shi & Zhengdong Zhang

  2. Department of Occupational Medicine and Environmental Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, 210029, China

    Haiyan Chu, Lan Ma, Meilin Wang, Danni Shi & Zhengdong Zhang

  3. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Chao Qin & Changjun Yin

  4. Department of Urology, Jiangsu Province Hospital of TCM, Nanjing, 210029, China

    Lin Yuan

Authors
  1. Haiyan Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lan Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Meilin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Danni Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chao Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lin Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Changjun Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhengdong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhengdong Zhang.

Additional information

Haiyan Chu, Lan Ma, and Meilin Wang should be regarded as joint first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chu, H., Ma, L., Wang, M. et al. The polymorphisms of IL-4, IL-4R and IL-13 genes and bladder cancer risk in a Chinese population: a case–control study. Mol Biol Rep 39, 5349–5357 (2012). https://doi.org/10.1007/s11033-011-1334-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-1334-9

Keywords

Search

Navigation