The DNA methylation of the interleukin6 as a biomarker for the early detection of colorectal cancer


  • Sakar Ahmed Abdullah Medical Laboratory Department, College of Health and Medical Technology, Sulaimani Polytechnic University, Sulaimani, Kurdistan, Iraq
  • Dlnya Assad Mohamad Department of Biology, College of Science, University of Sulaimani, Sulaymani, Kurdistan Region, Iraq



Colorectal cancer, DNA methylation, Epigenetic, Hypermethylation, Interleukin 6


Objectives: To identify the DNA methylation pattern of the interleukin6 promoter region in colorectal cancer patients and colorectal polys patients that could be a biomarker for early detection of colorectal cancer.

Methods: For this purpose, we examined the DNA methylation pattern of the promoter region of the IL6 specifically 358 bp (-292 to +67) including 7 CpG sites (-228, -213, -163, -119, +10, +19, +25) in a total of ninety samples with thirty samples each for controls, cancer patients, and colorectal polyps using the bisulfite conversion sequencing method.

Result: Our results indicate that CpG +25 and CpG -119 can serve as biomarkers for early detection of colon cancer, showing a significant difference in P-values of 0.001 at CpG +25 and 0.004 at CpG-119. The hypomethylation of CpG -119 in cancer groups facilitates the binding of the methyl-sensitive transcription factor Sp1. It enhances the overexpression of IL6 besides hypermethylation of CpG +25 that prevents binding of the methyl-sensitive insulator CTF, unbinding the insulator to the promoter region of the cancer samples makes the promoter region open access to the TFs that enhances overexpression. Furthermore, a remarkable non-recorded SNP at CpG -228 was observed in 98.6% of the enrolled groups.

Conclusion: In the state of DNA methylation, IL 6 could contribute to the onset of colorectal polyps and colorectal polyps cancer due to a significant level of methylation in CpG +25 and CpG -119.


Singal R, Ginder GD. DNA methylation. Blood, The Journal of the American Society of Hematology. 1999;93(12):4059-70.

Jin B, Robertson KD. DNA methyltransferases, DNA damage repair, and cancer. Epigenetic alterations in oncogenesis. 2012:3-29.

Gerecke C, Egea Rodrigues C, Homann T, Kleuser B. The role of ten-eleven translocation proteins in inflammation. Frontiers in immunology. 2022;13:1143.

Héberlé É, Bardet AF. Sensitivity of transcription factors to DNA methylation. Essays in biochemistry. 2019;63(6):727-41.

Douet V, Heller MB, Le Saux O. DNA methylation and Sp1 binding determine the tissue-specific transcriptional activity of the mouse Abcc6 promoter. Biochem Biophys Res Commun. 2007;354(1):66-71.

Damaschke NA, Gawdzik J, Avilla M, Yang B, Svaren J, Roopra A, et al. CTCF loss mediates unique DNA hypermethylation landscapes in human cancers. Clinical Epigenetics. 2020;12(1):1-13.

Knüpfer H, Preiß R. Significance of interleukin-6 (IL-6) in breast cancer. Breast cancer research and treatment. 2007;102:129-35.

Messeguer X, Escudero R, Farré D, Nuñez O, Martı́nez J, Albà MM. PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics. 2002;18(2):333-4.

Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23-38.

Giat E, Ehrenfeld M, Shoenfeld Y. Cancer and autoimmune diseases. Autoimmun Rev. 2017;16(10):1049-57.

Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nature reviews Gastroenterology & hepatology. 2019;16(12):713-32.

Gallo G, Kotze PG, Spinelli A. Surgery in ulcerative colitis: When? How? Best practice & research Clinical gastroenterology. 2018;32:71-8.

Waldner MJ, Foersch S, Neurath MF. Interleukin-6-a key regulator of colorectal cancer development. International journal of biological sciences. 2012;8(9):1248.

Gasche JA, Hoffmann J, Boland CR, Goel A. Interleukin‐6 promotes tumorigenesis by altering DNA methylation in oral cancer cells. Int J Cancer. 2011;129(5):1053-63.

Nile CJ, Read RC, Akil M, Duff GW, Wilson AG. Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum. 2008;58(9):2686-93.

Ryan J, Pilkington L, Neuhaus K, Ritchie K, Ancelin M-L, Saffery R. Investigating the epigenetic profile of the inflammatory gene IL-6 in late-life depression. Bmc Psychiatry. 2017;17:1-7.

Zhang H, Liu L, Fu S, Liu Y-S, Wang C, Liu T, et al. Higher platelet distribution width predicts poor prognosis in laryngeal cancer. Oncotarget. 2017;8(29):48138.

Li X-t, Yan Z, Wang R-t, Yu K-j. Preoperative mean platelet volume and platelet distribution width predict postoperative sepsis in patients with colorectal cancer. BioMed research international. 2019;2019.

Cheng S, Han F, Wang Y, Xu Y, Qu T, Ju Y, et al. The red distribution width and the platelet distribution width as prognostic predictors in gastric cancer. BMC gastroenterology. 2017;17:1-11.

Vulcan A, Manjer J, Ohlsson B. High blood glucose levels are associated with higher risk of colon cancer in men: a cohort study. BMC Cancer. 2017;17(1):1-8.

Saxena M, Agrawal C, Srivastava N, Banerjee M. Interleukin-6 (IL-6)-597 A/G (rs1800797) &-174 G/C (rs1800795) gene polymorphisms in type 2 diabetes. The Indian journal of medical research. 2014;140(1):60.




How to Cite

Ahmed Abdullah, S. ., & Assad Mohamad, D. . (2023). The DNA methylation of the interleukin6 as a biomarker for the early detection of colorectal cancer. Journal of Contemporary Medical Sciences, 9(6).