Journal of Gastrointestinal Cancer

, Volume 38, Issue 1, pp 46–51 | Cite as

Is IL-10 −819C/T Gene Polymorphism Modulating the Risk of Gallbladder Disease in North Indian Population?

Article
First Online:

Abstract

Background

Gallbladder carcinoma (GBC) is a highly aggressive neoplasm that arises in the background of gall stones and inflammation. Anti-inflammatory cytokine interleukin-10 (IL-10) gene polymorphisms have been associated with susceptibility to various inflammatory diseases and cancers.

Aim of the study

The aim of the present study was to investigate whether IL-10 −819C/T polymorphism is associated with GBC susceptibility.

Methods

The study subjects comprised 124 GBC patients, 135 patients with symptomatic gallstone disease, and 200 healthy subjects. Genomic DNA was extracted from blood leukocytes and IL-10 −819C/T gene polymorphism was analyzed by polymerase chain reaction–restriction fragment length polymorphism.

Results

Frequency distributions of IL-10 −819C/T genotypes were similar in GBC, gallstone patients, and healthy subjects. However, after stratification on the basis of sex, in male GBC patients, the TT genotype of IL-10 −819C/T polymorphism showed an approximately sevenfold risk (p value = 0.038; odds ratio = 6.58; 95% confidence interval = 1.11–39.11) in the presence of gall stones when compared with gallstone patients.

Conclusion

These results suggest that interplay of sex hormones and IL-10 −819C/T polymorphism may lead to the susceptibility of gallstone-mediated gallbladder carcinogenesis.

Keywords

IL-10 gallbladder carcinoma genetic susceptibility gallstones inflammation polymorphism 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgement

The study was supported by research grants from the Department of Science and Technology and the Indian Council of Medical Research, Government of India.

References

  1. 1.
    Chianale J, del Pino G, Nervi F. Increasing gall-bladder cancer mortality rate during the last decade in Chile, a high-risk area. Int J Cancer 1990;46:1131–3.PubMedCrossRefGoogle Scholar
  2. 2.
    Diehl AK. Gallstone size and the risk of gallbladder cancer. J Am Med Assoc 1983;250:2323–6.CrossRefGoogle Scholar
  3. 3.
    Bamba H, Ota S, Kato A, Matsuzaki F. Non-steroidal anti-inflammatory drugs may delay the repair of gastric mucosa by suppressing prostaglandin-mediated increase of hepatocyte growth factor production. Biochem Biophys Res Commun 1998;245:567–71.PubMedCrossRefGoogle Scholar
  4. 4.
    Indian Council of Medical Research (ICMR). Annual report of population based cancer registries of the National Cancer Registry Programme 1993. New Delhi: ICMR Publication; 1996. p. 18.Google Scholar
  5. 5.
    Lazcano-Ponce EC, Miquel JF, Munoz N, Herrero R, Ferrecio C, Wistuba II, Alonso de Ruiz P, Aristi Urista G, Nervi F. Epidemiology and molecular pathology of gallbladder cancer. Cancer J Clin 2001;51:349–64.CrossRefGoogle Scholar
  6. 6.
    Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumor. Nat Rev Cancer 2004;4:695–706.PubMedCrossRefGoogle Scholar
  7. 7.
    Macarthur M, Georgina LH, El-Omar EM. Inflammation and cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. Am J Physiol Gastrointest Liver Physiol 2004;286:515–20.CrossRefGoogle Scholar
  8. 8.
    Robert VR. Inflammatory cytokines alter human gallbladder epithelial cell absorption/secretion. J Gastrointest Surg 2000;4:185–92.CrossRefGoogle Scholar
  9. 9.
    Spits H, De Waal Malefyt R. Functional characterization of human IL-10. Int Arch Allergy Appl Immunol 1992;99:8–15.Google Scholar
  10. 10.
    Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997;24:1–8.PubMedGoogle Scholar
  11. 11.
    Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P. Polymorphic haplotypes of the interleukin-10 5′ flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 1999;42:1101–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Zambon CF, Basso D, Navaglia F, Belluco C, Falda A, Fogar P, Greco E, Gallo N, Rugge M, Di Mario F, Plebani, M. Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome. Cytokine 2005;29(4):141–52.PubMedCrossRefGoogle Scholar
  13. 13.
    Ioana Braicu E, Mustea A, Toliat MR, Pirvulescu C, Könsgen D, Sun P, Nürnberg P, Lichtenegger W, Sehouli J. Polymorphism of IL-1alpha, IL-1beta and IL-10 in patients with advanced ovarian cancer: results of a prospective study with 147 patients. Gynecol Oncol 2007;104(3):680–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Shih CM, Lee YL, Chiou HL, Hsu WF, Chen WE, Chou MC, Lin LY. The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer. Lung Cancer 2005;50(3):291–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Shiau MY, Huang CN, Yang TP, Hwang YC, Tsai KJ, Chi CJ, Chang YH. Cytokine promoter polymorphisms in Taiwanese patients with Graves’ disease. Clin Biochem 2007;40(3–4):213–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol 2003;4:167–76.PubMedCrossRefGoogle Scholar
  17. 17.
    Pandey SN, Modi DR, Choudhuri G, Mittal B. Slow acetylator genotype of N-Acetyl transferase2 (NAT2) is associated with increased susceptibility to gallbladder cancer: the cancer risk not modulated by gallstone disease. Cancer Biol Ther 2007;6(1):91–6.PubMedGoogle Scholar
  18. 18.
    Miller SA, Dykes DD, Polesky HF. A salting procedure for extracting DNA from nucleated cells. Nucleic Acids Res 1998;16:1215.CrossRefGoogle Scholar
  19. 19.
    Rad R, Dossumbekova A, Neu B, Lang R, Saur D, Gerhard M, Prinz C. Cytokine gene polymorphism influence mucosal expression, gastric inflammation, and host specific colonization during H. pylori infection. Gut 2004;53:1082–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Sykora J, Subrt I, Didek P, Siala K, Schwarz J, Machalova V, Varvarovska J, Pazdiora P, Pozler O, Stozicky F. Cytokine tumor necrosis factor-alpha a promoter gene polymorphism at position −308 G>A and pediatric inflammatory bowel disease: implications in ulcerative colitis and Crohn’s disease. J Pediatr Gastroenterol Nutr 2006;42(5):479–87.PubMedCrossRefGoogle Scholar
  21. 21.
    Lee JY, Kim HY, Kim KH, Kim SM, Jang MK, Park JY, Lee JH, Kim JH, Yoo JY. Association of polymorphism of IL-10 and TNF-A genes with gastric cancer in Korea. Cancer Lett 2005;225(2):207–14.PubMedCrossRefGoogle Scholar
  22. 22.
    Oppenheim J, Fujiwara H. The role of cytokines in cancer. Cytokine Growth Factor Rev 1996;7(3):279–88.PubMedCrossRefGoogle Scholar
  23. 23.
    Pretolani M, Stordeur P, Goldman M. Interleukin 10. In: Theze J, editor. The cytokine network and immune function. Oxford: Oxford University Press; 1999. p. 45–50.Google Scholar
  24. 24.
    Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response in humans. Hum Reprod Updat 2005;11(4):411–23.CrossRefGoogle Scholar
  25. 25.
    Ansar AS, Penhale WJ, Talal N. Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action. Am J Pathol 1985;121:531–51.Google Scholar
  26. 26.
    Cutolo M, Capellino S, Montagna P, Ghiorzo P, Sulli A. Villaggio sex hormone modulation of cell growth and apoptosis of the human monocytic/macrophage cell line. Arthritis Res Ther 2005;7(5):R1124–32.PubMedCrossRefGoogle Scholar
  27. 27.
    Dutta U, Garg PK, Kumar R, Tandon RK. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am J Gastroenterol 2000;95:784–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Nath G, Singh H, Shukla VK. Chronic typhoid carriage and carcinoma of the gallbladder. Eur J Cancer Prev 1997;6(6):557–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Leong RW, Sung JJ. Review article: helicobacter species and hepatobiliary diseases. Aliment Pharmacol Ther 2002;16(6):1037–45.PubMedCrossRefGoogle Scholar
  30. 30.
    Blazovics A. Gallstone disease: free radical reactions and the ambivalent role of bilirubin in the pathomechanism of gallstone formation. Orv Hetil 2007;148(13):589–96.PubMedCrossRefGoogle Scholar
  31. 31.
    Gupta SC, Misra V, Singh PA, Roy A, Misra SP, Gupta AK. Gall stones and carcinoma gall bladder. Indian J Pathol Microbiol 2000;43:147–54.PubMedGoogle Scholar
  32. 32.
    Zimnoch L, Szynaka B, Kupisz A. Study on carcinogenesis in chronic cholecystitis. Rocz Akad Med BiaLymst 2004;49:49–51.PubMedGoogle Scholar
  33. 33.
    Lowenfels AB, Lindstrom CG, Conway MJ, Hastings PR. Gallstones and risk of gallbladder cancer. J Natl Cancer Inst 1985;75:77–80.PubMedGoogle Scholar
  34. 34.
    Iwai N, Yanagihara J, Tokiwa K, Shimotake T, Nakamura K. Congenital choledochal dilatation with emphasis on pathophysiology of the biliary tract. Ann Surg 1992;215:27–30.PubMedCrossRefGoogle Scholar
  35. 35.
    Tanaka K, Nishimura A, Yamada K, Ishibe R, Ishizaki N, Yoshimine M, Hamada N, Taira A. Cancer of the gallbladder associated with anomalous junction of the pancreatobiliary duct system without bile dilation. Br J Surg 1993;80:622–4.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Monika Vishnoi
    • 1
  • Gourdas Choudhuri
    • 2
  • Balraj Mittal
    • 1
  1. 1.Department of GeneticsSanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia
  2. 2.Department of GastroenterologySanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia

Personalised recommendations