Skip to main content

Advertisement

Log in

Clinical Significance of Interleukin-6 (Il-6) Gene Polymorphism and Il-6 Serum Level in Pancreatic Adenocarcinoma and Chronic Pancreatitis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The aim of our study was to assess the clinical significance of -174G/C Il-6 gene polymorphism and Il-6 serum level in patients with pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP). The study included 41 with pancreatic adenocarcinoma, 56 with chronic pancreatitis, and 50 healthy volunteers, hospitalized between 2003 and 2006. Il-6 serum levels were measured with an enzyme-linked immunoassay and Il-6 gene polymorphism was studied in DNA isolated from peripheral blood. In PA and CP patients Il-6 serum levels were significantly higher than in the control group (P < 0.01). The levels of Il-6 in the patients with tumor size ≥3.5 cm were higher than that in patients with smaller tumors (P < 0.01). The elevated Il-6 levels were also correlated with the presence of liver metastases (P < 0.01). Mean Il-6 serum level was significantly higher in patients homozygous G/G for -174 Il-6 gene compared with patients with at least one C allele. Our findings indicate that -174G/C Il-6 gene polymorphism influences circulating Il-6 levels. Increased Il-6 serum levels may be correlated with tumor size and the presence of liver metastases in patients with pancreatic adenocarcinoma.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Lotz M (1993) Interleukin-6. Cancer Invest 11:732–742. doi:10.3109/07357909309046948

    Article  PubMed  CAS  Google Scholar 

  2. Ohzato H, Yoshizaki K, Nishimoto N, Ogata A, Tagoh H, Monden M et al (1992) Interleukin-6 as a new indicator of inflammatory status: detection of serum levels of interleukin-6 and C-reactive protein after surgery. Surgery 111:201–209

    PubMed  CAS  Google Scholar 

  3. Damas P, Ledoux D, Nys M, Wrindts Y, De Groote D, Franchimont P et al (1992) Cytokine serum level during severe sepsis in human Il-6 as a marker of severity. Ann Surg 215:356–362

    Article  PubMed  CAS  Google Scholar 

  4. Fishman D, Faulds G, Jeffery R, Mohamed-Ali U, Yudkin JS, Humpherces S (1998) The effect of novel polymorphisms in the interleukine-6 gene on Il-6 transcription and plasma Il-6 levels and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376. doi:10.1172/JCI2629

    Article  PubMed  CAS  Google Scholar 

  5. Dosquet C, Schaetz A, Faucher C, Lepage E, Wautier JL, Richard A et al (1994) Tumor necrosis factor-α, interleukin-1β and interleukin-6 in patients with renal cell carcinoma. Eur J Cancer 30:162–167. doi:10.1016/0959-8049(94)90079-5

    Article  Google Scholar 

  6. Okada S, Okusaka T, Ishii H, Kyogoku A, Yoshimori M, Kajimura N et al (1998) Elevated serum interleukin-6 levels in patients with pancreatic cancer. Jpn J Clin Oncol 28:12–15. doi:10.1093/jjco/28.1.12

    Article  PubMed  CAS  Google Scholar 

  7. Wu CW, Wang SR, Chao MF, Wu TC (1996) Serum interleukin-6 levels reflect disease status of gastric cancer. Am J Gastroenterol 91:1417–1422

    PubMed  CAS  Google Scholar 

  8. Lai R, O’Brien S, Maushouri T, Rogers A, Kantarijan H, Keating M et al (2002) Prognostic value of plasma interleukin-6 levels in patients with chronic lymphocytic leukemia. Cancer 95:1071–1075. doi:10.1002/cncr.10772

    Article  PubMed  CAS  Google Scholar 

  9. Takeda K, Fujii N, Nitta Y, Sakihara H, Nakyama K, Rikishi H et al (1991) Murine tumor cells metastasizing selectively in the liver: ability to produce hepatocyte-activating cytokines interleukin-1 and/or -6. Jpn J Cancer Res 82:1299–1308

    PubMed  CAS  Google Scholar 

  10. Tabibzadeh SS, Poubouridis D, May LT, Sehgal PB (1989) Interleukin-6 immunoreactivity in human tumors. Am J Pathol 135:427–433

    PubMed  CAS  Google Scholar 

  11. DeMichele A, Martin AM, Mick R, Gor P, Wray L, Klein-Cabral M et al (2003) Interleukin-6174 G/C polymorphism is associated with improved outcome in high-risk breast cancer. Cancer Res 63:8051–8056

    PubMed  CAS  Google Scholar 

  12. Nikiteas N, Tzanakis N, Gazouli M, Rallis G, Danilidis K, Theodoropoulus G et al (2005) Serum Il-6, TNF alpha and CRP levels in Greek colorectal cancer patients: prognosis implications. World J Gastroenterol 11:1639–1643

    PubMed  CAS  Google Scholar 

  13. Bowcock AM, Kidd JR, Lathrop GM, Daneshvar L, May L, Ray A et al (1988) The human “interferon-beta 2/hepatocyte stimulating factor/interleukin-6” gene: DNA polymorphism studies and localization to chromosome 7p21. Genomics 3:8–16. doi:10.1016/0888-7543(88)90152-8

    Article  PubMed  CAS  Google Scholar 

  14. Haddy N, Sass C, Maumus S, Marie B, Droesch S, Siest G, Visvikis S et al (2005) Biological variations, genetic polymorphisms and familial resemblance of TNF-alpha and Il-6 concentrations: STANISLAS cohort. Eur J Hum Genet 13:109–117. doi:10.1038/sj.ejhg.5201294

    Article  PubMed  CAS  Google Scholar 

  15. Hefler LA, Crimm C, Ackermann S, Malur S, Radjabi-Rahat AR, Leodolter S et al (2003) An interleukin-6 gene promoter polymorphism influences the biological phenotype of ovarian cancer. Cancer Res 63:3066–3068

    PubMed  CAS  Google Scholar 

  16. Belluco C, Olivieri F, Bonafe M, Giovagnetti S, Mammano E, Scalrta R et al (2003) 174G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res 9:2173–2176

    PubMed  CAS  Google Scholar 

  17. Barber MD, Powell JJ, Lynch SF, Fearon KH, Ross JA (2000) A polymorphism of the interleukin-1β gene influences survival in pancreatic cancer. Br J Cancer 83:1443–1447. doi:10.1054/bjoc.2000.1479

    Article  PubMed  CAS  Google Scholar 

  18. Ebrahimi B, Tucker SL, Li D, Abbruzzese JM, Kurzrock R (2004) Cytokines in pancreatic carcinoma. Correlation with phenotypic characteristics and prognosis. Cancer 101:2727–2736. doi:10.1002/cncr.20672

    Article  PubMed  CAS  Google Scholar 

  19. Sarner M, Cotton PB (1983) Classifications of pancreatitis. International Workshop, vol 25. King`s College, Cambridge, pp 756–759

    Google Scholar 

  20. Landi S, Moreno V, Gioia-Patricola L, Guino E, Navarro M, Oca J et al (2003) Association of common polymorphisms in inflammatory genes interleukin (Il)-6, Il-8, tumor necrosis factor alpha, NFKB1 and peroxisome proliferator-activated receptor γ with colorectal cancer. Cancer Res 63:3560–3566

    PubMed  CAS  Google Scholar 

  21. Goydos JS, Brumfield AM, Frezza E, Booth A, Lotze MT, Carty SE (1998) Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma. Ann Surg 227:398–404. doi:10.1097/00000658-199803000-00012

    Article  PubMed  CAS  Google Scholar 

  22. Bemelmans MA, Gouma DJ, Greve JW, Burman WA (1992) Cytokines, tumor necrosis factor and interleukin-6 in experimental biliary obstruction in mice. Hepatology 15:1132–1136. doi:10.1002/hep. 1840150626

    Article  PubMed  CAS  Google Scholar 

  23. Oka M, Yamamoto K, Takahashi M, Hakozaki M, Abe T, Lizuka N et al (1996) Relationship between serum levels of interleukin 6, various diseases parameters and malnutrition in patients with esophageal squamous cell carcinoma. Cancer Res 56:2776–2780

    PubMed  CAS  Google Scholar 

  24. Falconer JS, Fearon KC, Plester CE, Ross JA, Carter DC (1994) Cytokines, the acute-phase response and resting energy expenditure in cachectic patients with pancreatic cancer. Ann Surg 219:325–331. doi:10.1097/00000658-199404000-00001

    Article  PubMed  CAS  Google Scholar 

  25. Kinoshita T, Ito H, Miki C (1999) Serum interleukin-6 level reflects the tumor proliferative activity in patients with colorectal carcinoma. Cancer 85:2526–2531. doi:10.1002/(SICI)1097-0142(19990615)85:12<2526::AID-CNCR6>3.0.CO;2-3

    Article  PubMed  CAS  Google Scholar 

  26. Tanner J, Tosato G (1991) Impairment of natural killer functions by interleukin 6 increases lymphoblastoid cell tumorigenicity in athymic mice. J Clin Invest 88:239–247. doi:10.1172/JCI115283

    Article  PubMed  CAS  Google Scholar 

  27. Wigmore SJ, Fearon KC, Sangster K, Maingay JP, Garden OJ, Ross JA (2002) Cytokine regulation of constitutive production of interleukin-8 and -6 by human pancreatic cancer cell lines and serum cytokine concentrations in patients with pancreatic cancer. Int J Oncol 21:881–886

    PubMed  CAS  Google Scholar 

  28. Bhatnagar A, Wig JD, Majumdar S (2003) Immunological findings in acute and chronic pancreatitis. J Surg 73:59–64

    Google Scholar 

  29. Szuster-Ciesielska A, Daniluk J, Kandefer-Zerszen M (2000) Serum levels of cytokines in alcoholic liver cirrhosis and pancreatitis. Arch Immunol Ther Exp (Warsz) 48:301–307

    CAS  Google Scholar 

  30. Bomba T, Yoshioka U, Inoue H, Iwasaki Y, Hosoda S (1994) Serum levels of interleukin-1 beta and interleukin-6 in patients with chronic pancreatitis. J Gastroenterol 29:314–319. doi:10.1007/BF02358371

    Article  Google Scholar 

  31. Bonafe M, Olivieri F, Cavallone L, Giovagnetti S, Marchegiani F, Cardelli M et al (2001) A gender-dependent genetic predisposition to produce high levels of Il-6 is detrimental for longevity. Eur J Immunol 31:2357–2361. doi:10.1002/1521-4141(200108)31:8<2357::AID-IMMU2357>3.0.CO;2-X

    Article  PubMed  CAS  Google Scholar 

  32. Bendicho MT, Guedes JC, Silva NN, Santana GO, Sanot RR, Lyra AC et al (2005) Polymorphism of cytokine genes (TGF-beta1, INF-gamma, Il-6, Il-10 and TNF-alpha) in patients with chronic pancreatitis. Pancreas 30:333–336. doi:10.1097/01.mpa.0000161809.24284.33

    Article  PubMed  CAS  Google Scholar 

  33. Foster CB, Lehrnbecher T, Samuels S, Stein S, Mol F, Metcalf JA et al (2000) An Il-6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with immunodeficiency virus. Blood 96:2562–2567

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

Work supported by Medical University of Lodz, Poland grant 502-11-537.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Renata Talar-Wojnarowska.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Talar-Wojnarowska, R., Gasiorowska, A., Smolarz, B. et al. Clinical Significance of Interleukin-6 (Il-6) Gene Polymorphism and Il-6 Serum Level in Pancreatic Adenocarcinoma and Chronic Pancreatitis. Dig Dis Sci 54, 683–689 (2009). https://doi.org/10.1007/s10620-008-0390-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0390-z

Keywords

Navigation