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Significant association between interleukin-17A polymorphism and colorectal cancer

  • Research Article
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Tumor Biology

Abstract

Interleukin (IL) 17A is an inflammatory cytokine expressed by Th 17 cells and plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We have investigated the association between colorectal cancer and polymorphisms of IL17A (rs2275913. G197A). The study was performed in 241 subjects (102 with colorectal cancer and 139 healthy controls). Genotypes were determined by fluorescent-based restriction fragment length polymorphism method. The association between the molecular features at the gene in relation to tumor and patient clinical characteristics was analyzed. There was a significant difference between the genotype frequencies of IL17A G197A of control subjects (GG 68.34 % and GA + AA 31.65 %) and patients with colorectal cancer (GG 47.05 % and GA + AA 52.94 %) (p = 0.001with odds ratio (OR) 2.45 (1.43–4.11)). IL17A G197A polymorphism is particularly associated with colon cancer. Indeed, the IL17A GG genotype could be considered as a protective factor against colon cancer (p = 0.00001) with OR 3.77 (2.04–6.99). We have noted a significant association of IL17A G197A polymorphism not only with tumor localization (p = 0.003) but also with tumor differentiation (p = 0.0005) in CRC patients. We have also showed a significant association of G197A variant with an increased risk of advanced stage (p = 0.005). Our result suggests that the A allele of IL17A gene is involved in susceptibility to colorectal cancer and is associated with clinical features as tumor location, tumor differentiation, and TNM stage. IL17A polymorphism may serve as biomarker of disease location and progression.

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Abbreviations

CRC:

Colorectal cancer

IBD:

Inflammatory bowel disease

UC:

Ulcerative colitis

Th1/17 cells:

T helper 1/17 cells

IL17A/B/C/D/E/F:

Interleukin A/B/C/D/E/F

IL1β/6/8/10:

Interleukin IL1β/6/8/10

SNP:

Single nucleotide polymorphism

NF-κB:

Nuclear factor κB

TNFα:

Tumor necrosis factor α

TNM stage:

Tumor node metastasis stage

ETBF:

Enterotoxigenic Bacteroides fragilis

CIHM:

CpG island hyper-methylation

PR:

Progesterone receptor

VEFG:

Vascular endothelial growth factor

p53:

Tumor suppressor protein53

References

  1. Vasen HF, van der Meulen-de Jong AE, de Vos Tot Nederveen Cappel WH, Oliveira J. Familial colorectal cancer risk: ESMO clinical recommendations. Ann Oncol. 2009;20 Suppl 4:51–3.

    PubMed  Google Scholar 

  2. Carter AB, Misyak SA, Hontecillas R, Bassaganya-Riera J. Dietary modulation of inflammation-induced colorectal cancer through PPARgamma. PPAR Res. 2009;2009:498352.

    PubMed Central  PubMed  Google Scholar 

  3. Tanaka T. Development of an inflammation-associated colorectal cancer model and its application for research on carcinogenesis and chemoprevention. Int J Inflamm. 2012;2012:658786.

    Article  Google Scholar 

  4. Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer. 2001;91(4):854–62.

    Article  CAS  PubMed  Google Scholar 

  5. Lakatos PL, Lakatos L. Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J Gastroenterol. 2008;14(25):3937–47.

    Article  PubMed Central  PubMed  Google Scholar 

  6. 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(6):1202–6.

    Article  CAS  PubMed  Google Scholar 

  7. Erdman SE, Poutahidis T. Roles for inflammation and regulatory T cells in colon cancer. Toxicol Pathol. 2010;38(1):76–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–81.

    Article  CAS  PubMed  Google Scholar 

  9. Clevers H. At the crossroads of inflammation and cancer. Cell. 2004;118(6):671–4.

    Article  CAS  PubMed  Google Scholar 

  10. Sakamoto K, Maeda S, Hikiba Y, Nakagawa H, Hayakawa Y, Shibata W, et al. Constitutive NF-kappaB activation in colorectal carcinoma plays a key role in angiogenesis, promoting tumor growth. Clin Cancer Res. 2009;15(7):2248–58.

    Article  CAS  PubMed  Google Scholar 

  11. Wang S, Liu Z, Wang L, Zhang X. NF-kappaB signaling pathway, inflammation and colorectal cancer. Cell Mol Immunol. 2009;6(5):327–34.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 2007;117(5):1175–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Macarthur M, Hold GL, El-Omar EM. Inflammation and cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. Am J Physiol. 2004;286(4):G515–20.

    CAS  Google Scholar 

  14. Li M, You Q, Wang X. Association between polymorphism of the tumor necrosis factor alpha-308 gene promoter and colon cancer in the Chinese population. Genet Test Mol Biomark. 2011;15(11):743–7.

    Article  Google Scholar 

  15. Cen G, Wu W. Association between tumor necrosis factor-alpha 857C/T polymorphism and gastric cancer: a meta-analysis. Tumour Biol. 2013;47(9):1119–33.

    Google Scholar 

  16. Ito H, Kaneko K, Makino R, Konishi K, Kurahashi T, Yamamoto T, et al. Interleukin-1beta gene in esophageal, gastric and colorectal carcinomas. Oncol Rep. 2007;18(2):473–81.

    CAS  PubMed  Google Scholar 

  17. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000;404(6776):398–402.

    Article  CAS  PubMed  Google Scholar 

  18. Cacev T, Radosevic S, Krizanac S, Kapitanovic S. Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression. Carcinogenesis. 2008;29(8):1572–80.

    Article  CAS  PubMed  Google Scholar 

  19. Lu W, Pan K, Zhang L, Lin D, Miao X, You W. Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor alpha and risk of gastric cancer in a Chinese population. Carcinogenesis. 2005;26(3):631–6.

    Article  CAS  PubMed  Google Scholar 

  20. Landi S, Moreno V, Gioia-Patricola L, Guino E, Navarro M, de Oca J, et al. Association of common polymorphisms in inflammatory genes interleukin (IL)6, IL8, tumor necrosis factor alpha, NFKB1, and peroxisome proliferator-activated receptor gamma with colorectal cancer. Cancer Res. 2003;63(13):3560–6.

    CAS  PubMed  Google Scholar 

  21. Shibata T, Tahara T, Hirata I, Arisawa T. Genetic polymorphism of interleukin-17A and -17 F genes in gastric carcinogenesis. Hum Immunol. 2009;70(7):547–51.

    Article  CAS  PubMed  Google Scholar 

  22. McGovern DP, Rotter JI, Mei L, Haritunians T, Landers C, Derkowski C, et al. Genetic epistasis of IL23/IL17 pathway genes in Crohn’s disease. Inflamm Bowel Dis. 2009;15(6):883–9.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Yamada H. Current perspectives on the role of IL-17 in autoimmune disease. J Inflamm Res. 2010;3:33–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Kawaguchi M, Adachi M, Oda N, Kokubu F, Huang SK. IL-17 cytokine family. J Allergy Clin Immunol. 2004;114(6):1265–73. quiz 74.

    Article  CAS  PubMed  Google Scholar 

  25. Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21(4):467–76.

    Article  CAS  PubMed  Google Scholar 

  26. Kim SW, Kim ES, Moon CM, Park JJ, Kim TI, Kim WH, et al. Genetic polymorphisms of IL-23R and IL-17A and novel insights into their associations with inflammatory bowel disease. Gut. 2011;60(11):1527–36.

    Article  CAS  PubMed  Google Scholar 

  27. Zhang X, Yu P, Wang Y, Jiang W, Shen F, Wang Y, et al. Genetic polymorphisms of interleukin 17A and interleukin 17 F and their association with inflammatory bowel disease in a Chinese Han population. Inflamm Res. 2013;62(8):743–50.

    Article  CAS  PubMed  Google Scholar 

  28. Kim ES, Kim SW, Moon CM, Park JJ, Kim TI, Kim WH, et al. Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet’s disease in Korean population. Life Sci. 2012;90(19–20):740–6.

    Article  CAS  PubMed  Google Scholar 

  29. Nordang GB, Viken MK, Hollis-Moffatt JE, Merriman TR, Forre OT, Helgetveit K, et al. Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patients from Norway and New Zealand. Rheumatology (Oxford). 2009;48(4):367–70.

    Article  CAS  Google Scholar 

  30. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. The influence of polymorphisms of interleukin-17A and interleukin-17 F genes on the susceptibility to ulcerative colitis. J Clin Immunol. 2008;28(1):44–9.

    Article  CAS  PubMed  Google Scholar 

  31. Wu X, Zeng Z, Chen B, Yu J, Xue L, Hao Y, et al. Association between polymorphisms in interleukin-17A and interleukin-17 F genes and risks of gastric cancer. Int J Cancer. 2010;127(1):86–92.

    Article  CAS  PubMed  Google Scholar 

  32. Tahara T, Shibata T, Nakamura M, Yamashita H, Yoshioka D, Okubo M, et al. Effect of polymorphisms of IL-17A, -17 F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa. Int J Mol Med. 2009;24(4):563–9.

    Article  CAS  PubMed  Google Scholar 

  33. Quan Y, Zhou B, Wang Y, Duan R, Wang K, Gao Q, et al. Association between IL17 polymorphisms and risk of cervical cancer in Chinese women. Clin Dev Immunol. 2012;2012:258293.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Zhou B, Zhang P, Wang Y, Shi S, Zhang K, Liao H, et al. Interleukin-17 gene polymorphisms are associated with bladder cancer in a Chinese Han population. Mol Carcinog. 2012;52(11):871–8.

    Article  PubMed  Google Scholar 

  35. Steiner GE, Newman ME, Paikl D, Stix U, Memaran-Dagda N, Lee C, et al. Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate. 2003;56(3):171–82.

    Article  CAS  PubMed  Google Scholar 

  36. Zhu X, Mulcahy LA, Mohammed RA, Lee AH, Franks HA, Kilpatrick L, et al. IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines. Breast Cancer Res. 2008;10(6):R95.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Zhang B, Rong G, Wei H, Zhang M, Bi J, Ma L, et al. The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun. 2008;374(3):533–7.

    Article  CAS  PubMed  Google Scholar 

  38. Le Gouvello S, Bastuji-Garin S, Aloulou N, Mansour H, Chaumette MT, Berrehar F, et al. High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas. Gut. 2008;57(6):772–9.

    Article  PubMed  Google Scholar 

  39. Huber AK, Jacobson EM, Jazdzewski K, Concepcion ES, Tomer Y. Interleukin (IL)-23 receptor is a major susceptibility gene for Graves' ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity. J Clin Endocrinol Metab. 2008;93(3):1077–81.

    Google Scholar 

  40. Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res. 2011;71(4):1263–71.

    Article  CAS  PubMed  Google Scholar 

  41. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13(5):715–25.

    Article  CAS  PubMed  Google Scholar 

  42. Wang L, Jiang Y, Zhang Y, Wang Y, Huang S, Wang Z, et al. Association analysis of IL-17A and IL-17 F polymorphisms in Chinese Han women with breast cancer. PLoS ONE. 2012;7(3):e34400.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Suzuki H, Ogawa H, Miura K, Haneda S, Watanabe K, Ohnuma S, et al. IL-23 directly enhances the proliferative and invasive activities of colorectal carcinoma. Oncol Lett. 2012;4(2):199–204.

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci U S A. 2010;107(12):5540–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Tong Z, Yang XO, Yan H, Liu W, Niu X, Shi Y, et al. A protective role by interleukin-17 F in colon tumorigenesis. PLoS ONE. 2012;7(4):e34959.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank all the members of ‘Laboratoire Diagnostic Génétique et Moléculaire, Centre Jean Perrin, Clermont Ferrand, France for their technical assistance.

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Authors and Affiliations

  1. Laboratory of Human Genetics Immunology and Pathology, Faculty of Sciences Tunis, University of Tunis El Manar, El Manar, Tunis, 209, Tunisia

    Inés Omrane, Raja Marrakchi, Olfa Baroudi, Hager Ayari, Imen Medimegh, Nejla Stambouli, Hassen Bouzaienne, Karim Bougatef & Amel Benammar-Elgaaied

  2. Gastroenterology Service, Salah Azaiez Hospital of Tunis, Tunis, Tunisia

    Amel Mezlini

  3. Laboratory of Anatomy and Pathology, Charles Nicolle Hospital of Tunis, Tunis, Tunisia

    Nadia Kourda

  4. Laboratory of Diagnosis and Molecular Genetics, Centre Jean Perrin, Clermont-Ferrand, France

    Nancy Uhrhammer & Yves-Jean Jean Bignon

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  1. Inés Omrane
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Correspondence to Inés Omrane.

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Omrane, I., Marrakchi, R., Baroudi, O. et al. Significant association between interleukin-17A polymorphism and colorectal cancer. Tumor Biol. 35, 6627–6632 (2014). https://doi.org/10.1007/s13277-014-1890-4

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  • DOI: https://doi.org/10.1007/s13277-014-1890-4

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