Interleukin-1β, interleukin-6 and interleukin-10 polymorphisms in Tunisian patients with colorectal cancer and liver metastasis


  • Meriam Hazgui 1. Laboratory of Mycology, Pathologies and Biomarkers (LR16ES05), Faculty of Sciences of Tunis (FST), University of Tunis El Manar (UTM), Tunisia; 2. Colorectal Cancer Research Laboratory (UR12SP14), Mongi Slim Hospital, Marsa, Tunisia
  • Marwa Weslati 1. Colorectal Cancer Research Laboratory (UR12SP14), Mongi Slim Hospital, Marsa, Tunisia; 2. Laboratory of Molecular Genetics Immunology and Biotechnology (LR99ES12), Faculty of Sciences of Tunis (FST), University of Tunis El Manar (UTM), Tunisia
  • Donia Ounissi Laboratory of Neurophysiology, Cellular Physiopathology and Biomolecule Valorization (LR18ES03), Faculty of Sciences of Tunis (FST), University of Tunis El Manar (UTM), Tunisia
  • Rahma Boughriba Laboratory of Genetics Immunology and Human Pathology (LR05ES05), Faculty of Sciences of Tunis (FST), University of Tunis El Manar (UTM), Tunisia
  • Dhouha Bacha Colorectal Cancer Research Laboratory (UR12SP14), Mongi Slim Hospital, Marsa, Tunisia
  • Besma Yaacoubi Loueslati Laboratory of Mycology, Pathologies and Biomarkers (LR16ES05), Faculty of Sciences of Tunis (FST), University of Tunis El Manar (UTM), Tunisia



Colorectal cancer, liver metastasis, interleukins, gene polymorphism


Paper description:

  • Cytokines play an important role in cancer development.
  • Understanding genetic disparities improves prognosis and establishes more reliable diagnostic tests. We investigated the expression and gene variants of IL-1β, IL-6 and IL-10 in colorectal cancer and liver metastases.
  • The C/T genotype for IL-1β (-31C>T) increases colorectal cancer and liver metastasis risk; the C/A genotype for IL-10 (-592C>A) reduces both; the C/C genotype for IL-6 (-174G>C) increases liver metastasis risk.
  • Cytokine expression and gene variants can serve as biomarkers for early detection of both colorectal cancer and liver metastases and help predict overall patient survival.

Abstract: The balance between pro- and anti-inflammatory cytokine expression is essential for an efficient immune response and for the regulation of cancer development and progression. This study analyzed the expression and genetic variation in IL-1β, IL-6 and IL-10 genes and the possible associations with colorectal cancer (CRC) and colorectal liver metastases (CRLM).We examined IL-1β, IL-6 and IL-10 mRNA expression and three gene variants: IL-1β (rs1143627), IL-10 (rs1800872) and IL-6 (rs1800795), in 198 CRC, 65 CRLM patients and 230 controls. Carriers of the C/T genotype ofIL-1β (rs1143627) have an increased risk of developing CRC and CRLM. T/T genotype carriers have a higher risk of CRLM incidence. For IL-10 (rs1800872), patients harboring the C/A genotype have a lower risk of CRC and CRLM occurrence. For IL-6 (rs1800795), the C/C genotype heightens the risk of CRLM development. Overall survival analysis showed that carriers of the C/T genotype of IL-1β (rs1143627) have a worse overall survival in CRC patients. It can be concluded that interleukin genetic variants can be used as biomarkers to detect and predict clinical outcomes and prognostic factors for CRC and CRLM.


Download data is not yet available.


Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71(3):209-49.

Khiari H, Hsairi M. Colorectal cancer incidence and clinicopathological features in northern Tunisia 2007–2009. Colorectal Cancer. 2017;6(4):131‑41.

Khiari H, Ayoub HWB, Khadhra HB, Hsairi M. Colorectal Cancer Incidence Trend and Projections in Tunisia (1994 - 2024). Asian Pac J Cancer Prev APJCP. 2017;18(10):2733‑40.

Khiari H, Ayoub HWB, Khadhra HB, Hsairi M. Colorectal Cancer Incidence Trend and Projections in Tunisia (1994 - 2024). Asian Pac J Cancer Prev. 2017;18(10):2733‑40.

Valderrama-Treviño AI, Barrera-Mera B, C Ceballos-Villalva J, Montalvo-Javé EE. Hepatic Metastasis from Colorectal Cancer. Euroasian J Hepatogastroenterol. 2017;7(2):166‑75.

Pandith AA, Bhat I, Mansoor S, Koul A, Manzoor U, Anwar I, Mohammad F, Aein QU, Baba SM, Vladulescu C. Cytokine Gene Polymorphism and Cancer Risk: A Promising Tool for Individual Susceptibility and Prognostic Implications. In: Çalışkan M, editor. Genetic Polymorphisms - New Insights. London: IntechOpen; 2021. p.107-40.

Klampfer L. Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets. 2011;11(4):451‑64.

Li J, Huang L, Zhao H, Yan Y, Lu J. The Role of Interleukins in Colorectal Cancer. Int J Biol Sci. 14 juin 2020;16(13):2323‑39.

Bedoui S, Dallel M, Barbirou M, Stayoussef M, Mokrani A, Mezlini A, Bouhaouala B, Almawi WY, Yacoubi-Loueslati B. Interleukin-17A polymorphisms predict the response and development of tolerance to FOLFOX chemotherapy in colorectal cancer treatment. Cancer Gene Ther. 2020;27(5):311‑8.

Bedoui SA, Barbirou M, Stayoussef M, Dallel M, Mokrani A, Makni L, Mezlini A, Bouhaouala B, Yacoubi-Loueslati B, Almawi WY. Association of interleukin-17A polymorphisms with the risk of colorectal cancer: A case-control study. Cytokine. 2018;110:18‑23.

Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic Inflammation and Cytokines in the Tumor Microenvironment. J Immunol Res. 2014;2014:149185.

Bondurant KL, Lundgreen A, Herrick JS, Kadlubar S, Wolff RK, Slattery ML. Interleukin genes and associations with colon and rectal cancer risk and overall survival. Int J Cancer. 2013;132(4):905‑15.

Ayari JB, Guesmi R, Balti M, Ben Azaiz M, Zribi A, Fendri S, Ben Nasr S, Ghazouani E, Agili F, Kullab SA, Haddaoui A. Prognostic value of circulating cytokines in colorectal cancer: A prospective study in sixty colorectal cancer patients in Tunisia. JCO. 2019;37(15_suppl):e15130.

Mager LF, Wasmer MH, Rau TT, Krebs P. Cytokine-Induced Modulation of Colorectal Cancer. Front Oncol. 2016;6:96.

Elaraj DM, Weinreich DM, Varghese S, Puhlmann M, Hewitt SM, Carroll NM, Feldman ED, Turner EM, Alexander HR. The role of interleukin 1 in growth and metastasis of human cancer xenografts. Clin Cancer Res. 2006;12(4):1088‑96.

Komoda H, Tanaka Y, Honda M, Matsuo Y, Hazama K, Takao T. Interleukin-6 Levels in Colorectal Cancer Tissues. World J Surg. 1998;22(8):895‑8.

Maihöfner C, Charalambous MP, Bhambra U, Lightfoot T, Geisslinger G, Gooderham NJ, Colorectal Cancer Group. Expression of cyclooxygenase-2 parallels expression of interleukin-1beta, interleukin-6 and NF-kappaB in human colorectal cancer. Carcinogenesis. 2003;24(4):665‑71.

Chung YC, Chang YF. Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol. 2003;83(4):222‑6.

O’Hara RJ, Greenman J, MacDonald AW, Gaskell KM, Topping KP, Duthie GS, Kerin MJ, Lee PW, Monson JR. Advanced colorectal cancer is associated with impaired interleukin 12 and enhanced interleukin 10 production. Clin Cancer Res. 1998;4(8):1943‑8.

Stanilov N, Miteva L, Deliysky T, Jovchev J, Stanilova S. Advanced Colorectal Cancer Is Associated With Enhanced IL-23 and IL-10 Serum Levels. Laboratory Medicine. 2010;41(3):159‑63.

Belluco C, Olivieri F, Bonafè M, Giovagnetti S, Mammano E, Scalerta R, Ambrosi A, Franceschi C, Nitti D, Lise M. -174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res. 2003;9(6):2173‑6.

Bhat IA, Naykoo NA, Qasim I, Ganie FA, Yousuf Q, Bhat BA, Rasool R, Aziz SA, Shah ZA. Association of interleukin 1 beta (IL-1β) polymorphism with mRNA expression and risk of non small cell lung cancer. Meta Gene. 2014;2:123‑33.

Lowe PR, Galley HF, Abdel-Fattah A, Webster NR. Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients. Crit Care Med. 2003;31(1):34‑8.

Ikehara SK, Ikehara Y, Matsuo K, Hirose K, Niwa T, Ito H, Ito S, Kodera Y, Yamamura Y, Nakanishi H, Tatematsu M, Tajima K. A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population. J Hum Genet. 2006;51(11):927‑33.

Mirjalili SA, Moghimi M, Aghili K, Jafari M, Abolbaghaei SM, Neamatzadeh H, Mazaheri M, Zare-Shehneh M. Association of promoter region polymorphisms of interleukin-10 gene with susceptibility to colorectal cancer: a systematic review and meta-analysis. Arq Gastroenterol. 2018;55(3):306‑13.

Muñoz-Bellvis L, Fontanillo C, González-González M, Garcia E, Iglesias M, Esteban C, Gutierrez ML, Abad MM, Bengoechea O, De Las Rivas J, Orfao A, Sayagués JM. Unique genetic profile of sporadic colorectal cancer liver metastasis versus primary tumors as defined by high-density single-nucleotide polymorphism arrays. Mod Pathol. 2012;25(4):590‑601.

Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM, Meyer LR, Gress DM, Byrd DR, Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93‑9.

Hazgui M, Weslati M, Boughriba R, Ounissi D, Bacha D, Bouraoui S. MUC1 and MUC5AC implication in Tunisian colorectal cancer patients. Turk J Med Sci. 2021;51(1):309‑18.

Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system, Vol. 3. 4th ed. Lyon: International Agency for Research on Cancer; 2010. 13 p.

Wang S, Ding Z, Tang J, Li G. The association of interleukin-6 gene polymorphism and risk of colorectal cancer in Chinese patients. Transl Cancer Res 2018;7(2):401-410.

Harun-Or-Roshid M, Ali MB, Jesmin null, Mollah MNH. Statistical meta-analysis to investigate the association between the Interleukin-6 (IL-6) gene polymorphisms and cancer risk. PloS One. 2021;16(3):e0247055.

Wang P, An J, Zhu Y, Wan X, Zhang H, Xi S, Li S. Association of three promoter polymorphisms in interleukin-10 gene with cancer susceptibility in the Chinese population: a meta-analysis. Oncotarget. 2017;8(37):62382‑99.

Liu L, Zhai Z, Wang D, Ding Y, Chen X, Wang Q, Shu Z, Wu M, Chen L, He X, Fan D, Pan F, Xing M. The association between IL-1 family gene polymorphisms and colorectal cancer: A meta-analysis. Gene. 2020;769:145187.

Basavaraju U, Shebl F, Palmer A, Berry S, Hold G, El-Omar E, Rabkin C. Cytokine gene polymorphisms, cytokine levels and the risk of colorectal neoplasia in a screened population of Northeast Scotland. Eur J Cancer Prev. 2015;24(4):296‑304.

Banday MZ, Mir AH, Sameer AS, Chowdri NA, Haq E. Interleukin-1β (IL-1β) -31C/T and -511T/C promoter single nucleotide polymorphism in colorectal cancer in ethnic Kashmiri population - a case control study. Meta Gene. 2017;12:94‑103.

Liu C, Yuan ZY, Yuan H, Wu KX, Cao B, Ren KY, Cui MJ, Liu JH, Chen HX, Pang YW. Status of Gene Methylation and Polymorphism in Different Courses of Ulcerative Colitis and Their Comparison with Sporadic Colorectal Cancer. Inflamm Bowel Dis. 2021;27(4):522‑9.

Chen HX, Yuan ZY, Wu KX, Liu C, Mao QD, He BG, Yuan H. The study of methylation and single nucleotide polymorphisms of cancer-related genes in patients with early-stage ulcerative colitis. Scand J Gastroenterol. 2019;54(4):427‑31.

Liu J, Zhai X, Jin G, Hu Z, Wang S, Wang Xu, Qin J, Gao J, Ma H, Wang Xi, Wei Q, Shen H. Functional variants in the promoter of interleukin-1beta are associated with an increased risk of breast cancer: a case-control analysis in a Chinese population. Int J Cancer. 2006;118(10):2554‑8.

Ito LS, Iwata H, Hamajima N, Saito T, Matsuo K, Mizutani M, Iwase T, Miura S, Okuma K, Inoue M, Hirose K, Tajima K. Significant reduction in breast cancer risk for Japanese women with interleukin 1B -31 CT/TT relative to CC genotype. Jpn J Clin Oncol. 2002;32(10):398‑402.

Imen T, Messous S, Khouloud C, Grissa M, Kaouthar B, Nejia T, Imen G, Hamdi B, Riadh B, Wahid B, Mohamed Naceur S, Semir N. IL-1β gene polymorphism and serum levels in a Tunisian population with acute heart failure. Biomark Med. 2017;11:1069-76.

Banday MZ, Sameer AS, Chowdri NA, Haq E. Interleukin-10 −592C/A, but not −1082A/G promoter single nucleotide polymorphism, is associated with a decreased risk of colorectal cancer in an ethnic Kashmiri population: a case–control study. Eur J Cancer Prev. 2017;26(6):476‑90.

Ding Q, Shi Y, Fan B, Fan Z, Ding L, Li F, Tu W, Jin X, Wang J. The Interleukin-10 Promoter Polymorphism rs1800872 (-592C>A), Contributes to Cancer Susceptibility: Meta-Analysis of 16 785 Cases and 19 713 Controls. PLOS One. 2013;8(2):e57246.

Makni L, Ben Hamda C, Al-ansari A, Souiai O, Gazouani E, Mezlini A, Almawi W, Yacoubi Loueslati B. Association of common IL-10 promoter gene variants with the susceptibility to head and neck cancer in Tunisia. Turk J Med Sci. 2019;49(1):123‑8.

Sghaier I, Mouelhi L, Rabia NA, Alsaleh BR, Ghazoueni E, Almawi WY, Yacoubi Loueslati B. Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients. Cytokine. 2017;89:62‑7.

Landi S, Moreno V, Gioia-Patricola L, Guino E, Navarro M, de Oca J, Capella G, Canzian F, Bellvitge Colorectal Cancer Study Group. 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.

Peng X, Shi J, Sun W, Ruan X, Guo Y, Zhao L, Wang J, Li B. Genetic polymorphisms of IL-6 promoter in cancer susceptibility and prognosis: a meta-analysis. Oncotarget. 2018;9(15):12351‑64.

Theodoropoulos G, Papaconstantinou I, Felekouras E, Nikiteas N, Karakitsos P, Panoussopoulos D, Lazaris AC, Patsouris E, Bramis J, Gazouli M. Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer. World J Gastroenterol. 2006;12(31):5037‑43.

Banday MZ, Balkhi HM, Sameer AS, Chowdri NA, Haq E. Strong association of interleukin-6 -174G/C promoter single nucleotide polymorphism with a decreased risk of colorectal cancer in ethnic Kashmiri population: A case control study. Tumour Biol. 2017;39(3):1010428317695940.

Ghazouani L, Abboud N, Ben Hadj Khalifa S, Added F, Ben Khalfallah A, Nsiri B, Mediouni M, Mahjoub T. -174G>C interleukin-6 gene polymorphism in Tunisian patients with coronary artery disease. Ann Saudi Med. 2011;31(1):40‑4.

Hamzaoui A, Klii R, Harzallah O, Mahjoub T, Mahjoub S. Polymorphism of interleukin 6 -174 G/C in Behcet disease: case series and review of literature. Acta Med Iran. 2014;52(11):811‑5.

Cui G, Yuan A, Sun Z, Zheng W, Pang Z. IL-1β/IL-6 network in the tumor microenvironment of human colorectal cancer. Pathol Res Pract. 2018;214(7):986‑92.

Knüpfer H, Preiss R. Serum interleukin-6 levels in colorectal cancer patients--a summary of published results. Int J Colorectal Dis. 2010;25(2):135‑40.

Abdal-zahra N, Hamza SJ, Shamran HA, Al-Mayah QS. The significant of miR-196a2 C > T single nucleotide polymorphism and serum levels of Interleukin-1β (IL-1β) and Intrleukin-6 (IL-6) in colorectal cancer. J Pharm Sci Res. 2019;11(4):1652-6.

Caro GD, Carvello M, Pesce S, Erreni M, Marchesi F, Todoric J, Sacchi M, Montorsi M, Allavena P, Spinelli A. Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer. PLOS One. 2016;11(2):e0148186.

Wang P, Li C, Ma X, Gai X. Clinical significance of the combined measurement of serum B7-H1 and interleukin-10 in colorectal cancer patients. Medicine (Baltimore). 2020;99(18):e20044.

Qian H, Zhang D, Bao C. Two variants of Interleukin-1B gene are associated with the decreased risk, clinical features, and better overall survival of colorectal cancer: a two-center case-control study. Aging (Albany NY). 2018;10(12):4084‑92.

Csiszár A, Szentes T, Haraszti B, Balázs A, Petrányi GG, Pócsik E. The pattern of cytokine gene expression in human colorectal carcinoma. Pathol Oncol Res. 2004;10(2):109‑16.

Chung YC, Chaen YL, Hsu CP. Clinical significance of tissue expression of interleukin-6 in colorectal carcinoma. Anticancer Res. 2006;26(5B):3905‑11.

Zeng J, Tang ZH, Liu S, Guo SS. Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer. World J Gastroenterol. 2017;23(10):1780‑6.

Abtahi S, Davani F, Mojtahedi Z, Hosseini SV, Bananzadeh A, Ghaderi A. Dual association of serum interleukin-10 levels with colorectal cancer. J Cancer Res Ther. 2017;13(2):252‑6.




How to Cite

Hazgui M, Weslati M, Ounissi D, Boughriba R, Bacha D, Yaacoubi Loueslati B. Interleukin-1β, interleukin-6 and interleukin-10 polymorphisms in Tunisian patients with colorectal cancer and liver metastasis. Arch Biol Sci [Internet]. 2022Dec.21 [cited 2024Jul.20];74(4):333-45. Available from:




Most read articles by the same author(s)