Document Type : Original Article(s)


1 Department of Internal Medicine, Kosar Hospital, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

2 Social Determinants of Health Research Center, Semnan University of Medical Sciences, Semnan, Iran

3 Social Determinants of Health Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

4 Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Department of Physical Education and Sport Sciences, Islamic Azad University, Baneh Branch, Baneh, Iran


Background: Gastric cancer is one of the most prevalent ones with high incidence and mortality worldwide. The aim of this study was to determine the serum levels of tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) as potential diagnostic biomarkers in the first-degree relatives of patients with gastric cancer.
Method: The present work is a case-control study (case, n = 90; control, n = 90). The cases were selected from the first-degree relatives of the gastric cancer patients referred to Kosar Hospital of Semnan city, Iran, during 2019, consecutively. The controls were; however, a random sample from all the healthy people referred to Blood Transfusion Center of Semnan city in the same year. Demographic, laboratory, and pathological variables were collected from both groups. The levels of IL-6 and TNF-α were measured with ELISA method via platinum ELISA-8-11 kits. STATA 14 software was used for data analysis.
Results: In the case and control groups, 74.44 and 78.79% were male, respectively. Their mean age (SD) was 39.17 (10.75) and 36.16 (10.19) in the case and control groups, respectively. Based on the multivariable logistic regression model, there was a statistically significant difference between the two groups in terms of TNF-α (OR = 1.15; 95% confidence interval (CI): 1.02 – 1.30) and smoking (odds ratio (OR) = 3.57; 95% CI: 1.48 – 8.64). However, no statistically significant difference was seen between them concerning the level of IL-6 (OR = 1.0004; 95% CI: 0.97 – 1.03).
Conclusion: Increased levels of TNF-α might be useful as diagnostic biomarkers in the first-degree relatives of patients with gastric cancer; nonetheless, studies with larger sample size are required.


Hossein Nobakht (Google Scholar)

Farhad Malek (PubMed)


How to cite this article:

Nobakht H, Saghafi M, Ghorbani R, Mansori K, Fatemi SR, Allahmoradi M, et al. Evaluation of the serum levels of TNF-α and Interleukin-6 as potential diagnostic biomarkers in the first-degree relatives of patients with gastric cancer: a case-control study. Middle East J Cancer. 2023;14(3):428-35. doi: 10.30476/mejc.2022.94412.1724.

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492. Erratum in: CA Cancer J Clin. 2020;70(4):313.
  2. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global cancer Observatory: cancer today. [Internet] Lyon, France: International Agency for Research on Cancer. Cancer Today. [cited at: 2018]. Available on:
  3. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26-38. doi: 10.5114/pg.2018.80001.
  4. McColl KE, Going JJ. Aetiology and classification of adenocarcinoma of the gastro-oesophageal junction/cardia. Gut. 2010;59(3):282-4. doi: 10.1136/gut.2009.186825.
  5. Mukaisho K, Nakayama T, Hagiwara T, Hattori T, Sugihara H. Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids. Front Microbiol. 2015 11;6:412. doi: 10.3389/fmicb.2015.00412.
  6. Lauren P. The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31-49. doi: 10.1111/apm.1965.64.1.31.
  7. Nagini S. Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 2012;4(7):156-69. doi: 10.4251/wjgo.v4.i7.156.
  8. Hamajima N, Goto Y, Nishio K, Tanaka D, Kawai S, Sakakibara H, et al. Helicobacter pylori eradication as a preventive tool against gastric cancer. Asian Pac J Cancer Prev. 2004;5(3):246-52.
  9. Peek RM Jr, Fiske C, Wilson KT. Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol Rev. 2010;90(3):831-58. doi: 10.1152/physrev.00039.2009.
  10. Sánchez-Zauco N, Torres J, Gómez A, Camorlinga-Ponce M, Muñoz-Pérez L, Herrera-Goepfert R, et al. Circulating blood levels of IL-6, IFN-γ, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study. BMC Cancer. 2017;17(1):384. doi: 10.1186/s12885-017-3310-9. Erratum in: BMC Cancer. 2017;17 (1):669.
  11. Razavi A, Bagheri N, Azadegan-Dehkordi F, Shirzad M, Rahimian G, Rafieian-Kopaei M, et al. Comparative immune response in children and adults with H. pylori infection. J Immunol Res. 2015;2015:315957. doi: 10.1155/2015/315957.
  12. Israel DA, Peek RM. pathogenesis of Helicobacter pylori-induced gastric inflammation. Aliment Pharmacol Ther. 2001;15(9):1271-90. doi: 10.1046/j.1365-2036.2001.01052.x.
  13. Garza-González E, Bosques-Padilla FJ, El-Omar E, Hold G, Tijerina-Menchaca R, Maldonado-Garza HJ, et al. Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico. Int J Cancer. 2005;114(2):237-41. doi: 10.1002/ijc.20718.
  14. Ashizawa T, Okada R, Suzuki Y, Takagi M, Yamazaki T, Sumi T, et al. Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor. Gastric Cancer. 2005;8(2):124-31. doi: 10.1007/s10120-005-0315-x.
  15. Szczepanik AM, Scislo L, Scully T, Walewska E, Siedlar M, Kolodziejczyk P, et al. IL-6 serum levels predict postoperative morbidity in gastric cancer patients. Gastric Cancer. 2011;14(3):266-73. doi: 10.1007/s10120-011-0039-z.
  16. Foran E, Garrity-Park MM, Mureau C, Newell J, Smyrk TC, Limburg PJ, et al. Upregulation of DNA methyltransferase-mediated gene silencing, anchorage-independent growth, and migration of colon cancer cells by interleukin-6. Mol Cancer Res. 2010;8(4):471-81. doi: 10.1158/1541-7786.MCR-09-0496.
  17. Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell. 2009;15(2):103-13. doi: 10.1016/j.ccr.2009.01.001. Erratum in: Cancer Cell. 2009;15(3):241.
  18. Wang Z, Si X, Xu A, Meng X, Gao S, Qi Y, et al. Activation of STAT3 in human gastric cancer cells via interleukin (IL)-6-type cytokine signaling correlates with clinical implications. PLoS One. 2013;8(10):e75788. doi: 10.1371/journal.pone.0075788.
  19. Sugimoto M, Yamaoka Y, Furuta T. Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer. World J Gastroenterol. 2010;16(10):1188-200. doi: 10.3748/wjg.v16.i10.1188.
  20. Sethi G, Sung B, Aggarwal BB. TNF: a master switch for inflammation to cancer. Front Biosci. 2008;13:5094-107. doi: 10.2741/3066.
  21. Zhao C, Lu X, Bu X, Zhang N, Wang W. Involvement of tumor necrosis factor-alpha in the upregulation of CXCR4 expression in gastric cancer induced by Helicobacter pylori. BMC Cancer. 2010;10:419. doi: 10.1186/1471-2407-10-419.
  22. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001;104(4):487-501. doi: 10.1016/s0092-8674(01)00237-9.
  23. Wei ST, Sun YH, Zong SH, Xiang YB. Serum levels of IL-6 and TNF-α may correlate with activity and severity of rheumatoid arthritis. Med Sci Monit. 2015;21:4030-8. doi: 10.12659/msm.895116.
  24. Xu Y, Cao X, Jiang J, Chen Y, Wang K. TNF-α-308/-238 polymorphisms are associated with gastric cancer: A case-control family study in China. Clin Res Hepatol Gastroenterol. 2017;41(1):103-9. doi: 10.1016/j.clinre.2016.05.014.
  25. Yoon JH, Song JH, Kang YH, Park YK, Zhang C, Nam SW, et al. TNF-α and TNF-β polymorphisms with susceptibility to gastric cancer in a Korean population. Mol Cell Toxicol.  2010;6(2):161-7.