Investigating serum levels of IL-6 and TNF alpha, and the risk of thrombosis in newly diagnosed chemotherapy naïve obese cancer patients
Main Article Content
Keywords
Cancer , Inflammatory Cytokines , Obesity, Body Mass Index, Venous Thromboembolism
Abstract
Background: Obesity and cancer increase thrombosis risk. IL-6 and TNF-α, are key inflammatory cytokines, which may contribute to hypercoagulability in newly diagnosed, chemotherapy-naïve obese cancer patients, warranting further investigation. This study aimed to investigate the serum levels of these inflammatory biomarkers and risk of VTE in chemotherapy naïve obese cancer patients (CNOCPs).
Methodology: The study was cross-sectional analytical in design. The participants consisted of newly diagnosed patients with solid malignancies recruited from adult oncology clinics of a Nigerian tertiary hospital. They were grouped into two: case group (n = 37) consisting of chemotherapy naïve OCPs and control group (n = 63) consisting of chemotherapy naïve non-OCPs Patients were risk assessed using the Khorana scoring system. All the patients’ serum samples were assayed by ELISA technique for IL-6 and TNF-α. History of VTE was obtained from the patients’ case notes and by direct interviews with the patients.
Results: The mean age of the participants was 48.44±13.4 (range = 20 – 76) years, and the mean BMI was 26.80±6.3Kg/m2. The mean levels of IL-6 and TNF-α were significantly higher in chemotherapy naïve OCPs than the controls (7.9 ± 1.2 vs. 6.5 ±1.2, p < 0.001 and 5.2 ± 2.3 vs. 4.1 ± 1.9, p = 0.012 respectively. Also, chemotherapy naïve OCPs had a three-fold higher risk of VTE than the controls (OR: 3.0; 95% CI: 1.1-7.5; p= 0.03).
Conclusion: The inflammatory biomarkers were significantly higher in chemotherapy naïve OCPs than the non-obese controls. Additionally, they are at higher risk of VTE. These findings could strengthen clinicians’ disposition for prompt initiation of thromboprophylaxis in OCPs.
References
2. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. J Am Med Asso 2012; 311:806–814.
3. Adenuga, Adedire Timilehin; Salu, Iliya Karniliyus1; Bello, Usman Mohammed2; Okaro, Abuchi3. Obesity and the Need for Bariatric Surgery in Nigeria: A Review. Nigerian Postgraduate Medical Journal 31(3):p 207-212, Jul–Sep 2024. | DOI: 10.4103/npmj.npmj_157_24
4. Zhong W, Wang X, Wang Y, Sun G, Zhang J, Li Z. Obesity and endocrine-related cancer: The important role of IGF-1. Front Endocrinol (Lausanne). 2023;14:1093257
5. Liang X, Wang S, Wang X, Zhang L, Zhao H, Zhang L. Leptin promotes the growth of breast cancer by upregulating the Wnt/Beta-catenin pathway. Exp Ther Med 2018; 16(2):767–71
6. Kakugawa Y, Tada H, Kawai M, Suzuki T, Nishino Y, Kanemura S, et al. Associations of obesity and physical activity with serum and intratumoral sex steroid hormone levels among postmenopausal women with breast cancer: Analysis of paired serum and tumor tissue samples. Breast Cancer Res Treat. 2017; 162(1):115–25
7. Carobbio S, Pellegrinelli V, Vidal-Puig A. Adipose Tissue Function and Expandability as Determinants of Lipotoxicity and the Metabolic Syndrome. Adv Exp Med Biol. 2017; 960:161-196
8. Pellegrinelli V, Carobbio S, Vidal-Puig A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia. 2016;59(6):1075-88
9. Center for disease control. Obesity and cancer. (2025). Available at https://www.cdc.gov/cancer/risk-factors/obesity.html. Last accessedon 21st May, 2025
10. Chukwuonye II, Ohagwu KA, Ogah OS, John C, Oviasu E, Anyabolu EN, et al. Prevalence of overweight and obesity in Nigeria: systematic review and meta-analysis of population-based studies. PLOS Glob Public Health 2022; 2(6):e0000515.
11. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet. 2008; 371(9612):569–578
12. De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. J Obes 2013;2013:291546
13. Shuster A, Patlas M, Pinthus JH, Mourtzakis M. The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. Br J Radiol. 2012; 85(1009):1-10.
14. López-Soriano FJ, Argilés JM. Obesity and inflammation: A complex relationship. Curr Diabetes Rev. 2020;16(5):464-74. doi:10.2174/1573399816666200526125409.
15. O'Sullivan J, Lysaght J, Donohoe CL, Reynolds JV. Obesity and gastrointestinal cancer: the interrelationship of adipose and tumour microenvironments. Nat Rev Gastroenterol Hepatol. 2018 Nov;15(11):699-714. doi: 10.1038/s41575-018-0069-7.
16. Hopkins BD, Goncalves MD, Cantley LC. Obesity and Cancer Mechanisms: Cancer Metabolism. J Clin Oncol. 2016 Dec 10;34(35):4277-4283. doi: 10.1200/JCO.2016.67.9712
17. Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation. J Clin Oncol. 2016 Dec 10;34(35):4270-4276. doi: 10.1200/JCO.2016.67.4283.
18. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K; International Agency for Research on Cancer Handbook Working Group. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug 25;375(8):794-8. doi: 10.1056/NEJMsr16066024o
19. Sato Y, Tsujinaka S, Miura T, Kitamura Y, Suzuki H, Shibata C. Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management. Cancers (Basel). 2023 Aug 17;15(16):4154. doi: 10.3390/cancers15164154
20. Annett S, Moore G, Robson T. Obesity and Cancer Metastasis: Molecular and Translational Perspectives. Cancers 2020;12:3798.
21. Mohammadi M, Gozashti MH, Aghadavood M, Mehdizadeh MR, Hayatbakhsh MM. Clinical Significance of Serum IL-6 and TNF-α Levels in Patients with Metabolic Syndrome. Rep Biochem Mol Biol. 2017;6(1):74-79
22. Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood. 2013 Nov 14;122(20):3415-22. doi: 10.1182/blood-2013-05-427708
23. Blokhin IO, Lentz SR. Mechanisms of thrombosis in obesity. Curr Opin Hematol. 2013 Sep;20(5):437-44. doi: 10.1097/MOH.0b013e3283634443
24. Cyr AR, Huckaby LV, Shiva SS, Zuckerbraun BS. Nitric Oxide and Endothelial Dysfunction. Crit Care Clin. 2020 Apr;36(2):307-321. doi: 10.1016/j.ccc.2019.12.009
25. Broni EK, Ogunmoroti O, Quispe R, Sweeney T, Varma B, Fashanu OE, Lutsey PL, Matthew Allison, Moyses Szklo, Ndumele CE, Michos ED. Adipokines and incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis. J Thromb Haemost. 2023 Feb;21(2):303-310. doi: 10.1016/j.jtha.2022.11.012.
26. Halsema K, Mcmahon B. Cancer-Associated Thrombosis: Risk Assessment, Prevention, and Treatment. J Adv Pract Oncol. 2023; 14(3):213-217
27. Mulder FI, Candeloro M, Kamphuisen PW, Di Nisio M, Bossuyt PM, Guman N, et al; CAT-prediction collaborators. The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis. Haematologica. 2019;104(6):1277-1287
28. Divella R, De Luca R, Abbate I, Naglieri E, Daniele A. Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation. J Cancer. 2016;7(15):2346-2359
29. Aydin Y, Kaplan I, Bilen Y, Bulut C, Genc F, Turkyilmaz A, et al Plasma levels of IL-6 and TNF-α in patients with esophageal cancer Turk J Med Sci. 2012;42:762–7
30. Michalaki, V., Syrigos, K., Charles, P. et al. Serum levels of IL-6 and TNF-α correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer 90, 2312–2316 (2004). https://doi.org/10.1038/sj.bjc.6601814
31. Ageno W, Bertù L, Bucherini E, Camporese G, Dentali F, Iotti M, Lessiani G, Parisi R, Prandoni P, Sartori M, Visonà A, Bigagli E, Palareti G; RIDTS study group. Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial. BMJ. 2022 Nov 23;379:e072623. doi: 10.1136/bmj-2022-072623.
32. Glise Sandblad K, Jern S, Åberg M, Robertson J, Torén K, Lindgren M, Adiels M, Hansson PO, Rosengren A. Obesity in adolescent men increases the risk of venous thromboembolism in adult life. J Intern Med. 2020 Jun;287(6):734-745. doi: 10.1111/joim.13044
33. Hotoleanu C. Association between obesity and venous thromboembolism. Med Pharm Rep. 2020; 93(2):162-168.
34. Stein PD. Obesity as a risk factor in venous thromboembolism. In Stein PD (ed). Pulmonary embolism, 3rd Edition. John Wiley & Sons, Ltd; 2016: pp. 133-138.
35. El-Menyar A, Asim M, Al-Thani H. Obesity Paradox in Patients With Deep Venous Thrombosis. Clin Appl Thromb Hemost. 2018; 24:986-992.
36. Lee H. Obesity-Associated Cancers: Evidence from Studies in Mouse Models. Cells. 2022 Apr 27;11(9):1472. doi: 10.3390/cells11091472
37. Hansda S, Das H. Insights into Cancer-Associated Thrombosis Leading Towards Ischemic Stroke. Biology (Basel). 2025 Jan 10;14(1):50. doi: 10.3390/biology14010050.
38. Farge D, Frere C, Connors JM, Ay C, Khorana AA, Munoz A, et al. International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2019; 20(10):e566-e581
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
This is an open-access journal and articles are distributed under the terms of the Creative Commons Attribution Non-Commercial Share-Alike License 4.0. This licence allows users to download and share, remix, tweak and build upon the article for non-commercial purposes, so long as the original authorship is acknowledged and the new creations are licensed under identical terms.
Angela Ogechukwu Ugwu, Department of Haematology and Immunology, Faculty of Basic clinical Sciences, College of Medicine, University of Nigeria Ituku/Oza[la, Enugu
Asociate Professor and Consultant Haematologist, Department of Haematology and Immunology, Faculty of Basic clinical Sciences, College of Medicine, University of Nigeria Ituku/Oza[la, Enugu, Nigeria
Ifeyinwa Dorothy Nnakenyi, Department of Chemical Pathology, Faculty of Basic clinical Sciences, College of Medicine, University of Nigeria Ituku/Ozalla, Enugu, Nigeria
Senior Lecturer and Consultant Chemical Pathologist, Department of Chemical Pathology, Faculty of Basic clinical Sciences, College of Medicine, University of Nigeria Ituku/Ozalla, Enugu, Nigeria.
Chika Juliet Okwor, Department of Chemical Pathology, Faculty of Basic clinical Sciences, College of Medicine, University of Nigeria Ituku/Ozalla, Enugu, Nigeria
Senior Lecturer and Consultant Chemical Pathologist, Department of Chemical Pathology, Faculty of Basic clinical Sciences, College of Medicine, University of Nigeria Ituku/Ozalla, Enugu, Nigeria