Document Type : Research articles


1 Department of Social Medicine, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran

2 Department of Surgery, Qom University of Medical Sciences, Qom, Iran

3 Departments of Biostatistics, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

4 Student Research Committee, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran

5 1.Department of Physiology and Pharmacology, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran 2.Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran


Background: Despite clinical and basic different investigations, the role of plasma adipokines, such as adiponectin as a precise predictor of the risk of colorectal cancer (CRC) is still conflicting.
Aim: This study investigated the association between CRC and insulin resistance, obesity, and plasma adiponectin level for the first time in Iran.
Method: A total of 80 subjects (including 45 CRC patients and 35 healthy individuals) were enrolled in this case-control study. Demographic, anthropometric, and clinical data were recorded, and serum levels of adiponectin, insulin, and glucose were evaluated using enzyme-linked immunosorbent assay and glucose oxidase technique, respectively. Insulin resistance index (HOMA-IR) was measured as well.
Results: The mean±SD plasma adiponectin concentration of the CRC patients (7.98±0.64 ng/ml) was not significantly higher, compared to that in the control group (8.05±1.14 ng/mL). The mean±SD of HOMA-IR and plasma glucose levels (1.81±0.61 and 7.64±1.34 mm/L, respectively) of the CRC group were significantly higher (P<0.05), compared to the control group (1.37±0.3 and 119±1.1 mg/dL, respectively); however, plasma insulin wasnt significantly different in the two study groups. Following the stratification of CRC patients according to the tumor site, a significantly lower level of adiponectin (7.36 ±1.1 ng/ml) (P<0.05) and a significantly higher level of HOMA-IR (2.08±0.44) were observed in patients with colon cancer (P<0.005), compared to the controls. Regression among the plasma adiponectin and the plasma insulin and HOMA was negative in the control and CRC groups.
Conclusion: Insulin resistance has an important role in the development of CRC, especially in genesis colon cancer, regardless of the change that it causes in plasma levels of adiponectin.


  1. Mahmoudi T, Majidzadeh AK, Karimi K, Karimi N, Farahani H, Dabiri R, et al. An exon variant in insulin receptor gene is associated with susceptibility to colorectal cancer in women. Tumor Biol. 2015;36(5):3709-15. doi: 10.1007/s13277-014-3010-x.
  2. Benson AB, 3rd. Epidemiology, disease progression, and economic burden of colorectal cancer. J Manag Care Pharm. 2007;13(6 Suppl C):S5-18. doi: 10.18553/jmcp.2007.13.s6-c.5. [PMID: 17713990]
  3. Mahmoudi T, Farahani H, Nobakht H, Dabiri R, Zali MR. Genetic variations in leptin and leptin receptor and susceptibility to colorectal cancer and obesity. Iran J Cancer Prev. 2016;9(3):e7013. doi: 10.17795/ijcp-7013. [PMID: 27703650]
  4. Mahmoudi T, Majidzadeh-A K, Karimi K, Farahani H, Dabiri R, Nobakht H, et al. Gly972Arg variant of insulin receptor substrate 1 gene and colorectal cancer risk in overweight/obese subjects. Int J Biol Markers. 2016;31(1):68-72. doi: 10.5301/jbm.5000159. [PMID: 26349669]
  5. Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi RE, Corcione F. Worldwide burden of colorectal cancer: a review. Updates Surg. 2016;68(1):7-11. doi: 10.1007/s13304-016-0359-y. [PMID: 27067591]
  6. Mahmoudi T, Karimi K, Arkani M, Farahani H, Vahedi M, Dabiri R, et al. Resistin -420C>G promoter variant and colorectal cancer risk. Int J Biol Markers. 2014;29(3):e233-8. doi: 10.5301/jbm.5000079. [PMID: 30379922]
  7. John B, Irukulla S, Abulafi A, Kumar D, Mendall M. Systematic review: adipose tissue, obesity and gastrointestinal diseases.       Aliment Pharmacol Ther. 2006;23(11):1511-23. doi: 10.1111/j.1365-2036.2006.02915.x.
  8. Limburg PJ, Stolzenberg-Solomon RZ, Vierkant RA, Roberts K, Sellers TA, Taylor PR, et al. Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers. Clin Gastroenterol Hepatol. 2006;4(12):1514-21. doi: 10.1016/j.cgh.2006.09.014. [PMID: 17162243]
  9. Farahani H, Mahmoudi T, Asadi A, Nobakht H, Dabiri R, Hamta A. Insulin resistance and colorectal cancer risk: the role of elevated plasma resistin levels. J Gastrointest Cancer. 2020;51(2):478-83. doi: 10.1007/s12029-019-00260-7. [PMID: 31168777]
  10. Chang C, Ulrich C. Hyperinsulinaemia and hyperglycaemia: possible risk factors of colorectal cancer among diabetic patients. Diabetologia. 2003;46(5):595-607. doi: 10.1007/s00125-003-1109-5. [PMID: 12764580]
  11. Kaaks R. Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control. 1996;7(6):605-25. doi: 10.1007/BF00051703. [PMID: 8932921]
  12. Sandhu MS, Dunger DB, Giovannucci EL. Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst. 2002;94(13):972-80. doi: 10.1093/jnci/94.13.972. [PMID: 12096082]
  13. Scharf J, Ramadori G, Braulke T, Hartmann H. Synthesis of insulinlike growth factor binding proteins and of the acid‐labile subunit in primary cultures of rat hepatocytes, of Kupffer cells, and in cocultures: Regulation by insulin, insulinlike growth factor, and growth hormone. Hepatology. 1996;23(4):818-27. doi: 10.1053/jhep.1996.v23.pm0008666337.
  14. Mahmoudi T, Karimi K, Karimi N, Farahani H, Nobakht H, Dabiri R, et al. Association of adiponectin receptor 1 gene− 106 C> T variant with susceptibility to colorectal cancer. Meta Gene. 2016;9:210-4. doi: 10.1016/j.mgene.2016.07.008.
  15. Kelesidis I, Kelesidis T, Mantzoros C. Adiponectin and cancer: a systematic review. Br J Cancer. 2006;94(9):1221-5. doi: 10.1038/sj.bjc.6603051. [PMID: 16570048]
  16. Chandler PD, Buring JE, Manson JE, Moorthy M, Zhang S, Lee I-M, et al. Association between plasma adiponectin levels and colorectal cancer risk in women. Cancer Causes Control. 2015;26(7):1047-52. doi: 10.1007/s10552-015-0590-8. [PMID: 25941065]
  17. Cavagnari MAV, Vidigal VM, Silva TD, Barão K, Forones NM. Adiponectin, vitamin D and nutritional status in patients with advanced colorectal cancer or during follow-up. Arq Gastroenterol. 2019;56:172-7. doi: 10.1590/S0004-2803.201900000-34. [PMID: 31460582]
  18. Świerczyński M, Szymaszkiewicz A, Fichna J, Zielińska M. New insights into molecular pathways in colorectal cancer: Adiponectin, interleukin-6 and opioid signaling. Biochim Biophys Acta Rev Cancer. 2021;1875(1):188460. doi: 10.1016/j.bbcan.2020.188460. [PMID: 33184028]
  19. Hajri T, Tao H, Wattacheril J, Marks-Shulman P, Abumrad NN. Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6. Am J Physiol Endocrinol Metab. 2011;300(2):E350-E60. doi: 10.1152/ajpendo.00307.2010. [PMID: 21062957]
  20. Demir N, Ahishali E, Dolapcioglu C, Ercan S, Orcun Kaptanagasi A, Dabak R, et al. The relationship between serum adiponectin and resistin levels, insulin resistance and colorectal adenomas. Turk J Gastroenterol. 2015;26(1):20-4. doi: 10.5152/tjg.2015.3626. [PMID: 25698266]
  21. Gonullu G, Kahraman H, Bedir A, Bektas A, Yücel I. Association between adiponectin, resistin, insulin resistance, and colorectal tumors. Int J Colorectal Dis. 2010;25(2):205-12. doi: 10.1016/j.metabol.2018.11.001. [PMID: 19888587]
  22. An W, Bai Y, Deng S-X, Gao J, Ben Q-W, Cai Q-C, et al. Adiponectin levels in patients with colorectal cancer and adenoma: a meta-analysis. Eur J Cancer Prev. 2012;21(2):126-33. doi: 10.1097/CEJ.0b013e32834c9b55. [PMID: 21960184]
  23. Otani K, Ishihara S, Yamaguchi H, Murono K, Yasuda K, Nishikawa T, et al. Adiponectin and colorectal cancer. Surg Today. 2017;47(2):151-8. doi: 10.1016/j.metabol.2018.11.001. [PMID: 27061803]
  24. Asadi A, Farahani H, Mahmoudi T, Tabaeian SP, Rezamand G, Mohammadbeigi A, et al. circulating ghrelin levels and susceptibility to colorectal câncer. Arq Gastroenterol. 2021;58(3):316-21. doi: 10.1590/S0004-2803.202100000-54 [PMID: 34705965]
  25. Farahani H, Ghasemi A, Roghani M, Zahediasl S. Effect of neonatal hypothyroidism on carbohydrate metabolism, insulin secretion, and pancreatic islets morphology of adult male offspring in rats. J Endocrinol Invest. 2013;36(1):44-9. doi: 10.1055/s-0030-1262826. [PMID: 22732210]
  26. Chen MW, Ye S, Zhao LL, Wang SY, Li YX, Yu CJ, et al. Association of plasma total and high-molecular-weight adiponectin with risk of colorectal cancer: an observational study in Chinese male. Med Oncol. 2012;29(5):3129-35. doi: 10.1007/s12032-012-0280-2. [PMID: 22752603]
  27. Xu XT, Xu Q, Tong JL, Zhu MM, Huang ML, Ran ZH, et al. Meta-analysis: circulating adiponectin levels and risk of colorectal cancer and adenoma. J Dig Dis. 2011;12(4):234-44. doi: 10.1111/j.1751-2980.2011.00504.x. [PMID: 21791018]
  28. Chakraborty D, Jin W, Wang J. The bifurcated role of adiponectin in colorectal cancer. Life Sci. 2021;278:119524. doi: 10.1016/j.lfs.2021.119524. [PMID: 33887344]