Skip to main content

Insulin resistance and risk of renal cell cancer: a case-control study



Obesity and diabetes are considered risk factors for Renal Cell Carcinoma (RCC). We aimed to explore whether insulin resistance (IR) plays an independent role in the development of RCC.


In a hospital-based case-control study, we analyzed serum glucose, insulin, leptin and adiponectin levels among 60 incident RCC patients and 236 age- and gender-matched healthy controls. We assessed insulin resistance according to insulin levels, alone or controlled for diabetes mellitus (DM). An alternative measure of insulin resistance, such as the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index, was also assessed with and without controlling for history of DM. We used logistic regression to estimate odds ratios (ORs) adjusted for possible confounders.


The positive association of DM and waist to hip ratio as a measure of obesity with RCC was evident in the data set. Insulin levels controlled or not controlled for DM, however, were inversely associated with the risk for RCC; notably, an approximately 40% higher risk was observed in the 1st tertile when compared with the 2nd and 3rd tertile levels of insulin resistance. Similar results were obtained when HOMA-IR was alternatively used. The inverse associations persisted and were even strengthened after controlling for potential confounding factors in multivariate analyses.


Our data suggest that insulin resistance may be inversely associated with RCC risk, independently of obesity, DM, lifestyle and hormonal confounding variables. Given the close interconnections among metabolic, inflammatory and immune pathways in RCC causation, it is difficult to infer which process actually initiates a pathologic cascade. The findings should be considered as preliminary data that need to be further confirmed in more appropriate study designs.


  1. 1

    Adami HO, McLaughlin J, Ekbom A, et al, 1991 Cancer risk in patients with diabetes mellitus. Cancer Causes Control 2: 307–314.

    Article  CAS  Google Scholar 

  2. 2

    Lindblad P, Chow WH, Chan J, et al, 1999 The role of diabetes mellitus in the aetiology of renal cell cancer. Diabetologia 42: 107–112.

    Article  CAS  Google Scholar 

  3. 3

    Cho E, Adami HO, Lindblad P, 2011 Epidemiology of Renal Cell Cancer. Hematol Oncol Clin N Am 25: 651–665.

    Article  Google Scholar 

  4. 4

    Chow WH, Dong LM, Devesa SS, 2010 Epidemiology and risk factors for kidney cancer. Nat Rev Urol 7: 245–257.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5

    Godsland IF, 2009 Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clin Sci (Lond) 118: 315–332.

    Article  CAS  Google Scholar 

  6. 6

    Tilg H, Moschen AR, 2006 Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6: 772–783.

    Article  CAS  Google Scholar 

  7. 7

    Gil A, María Aguilera C, Gil-Campos M, Cañete R, 2007 Altered signalling and gene expression associated with the immune system and the inflammatory response in obesity. Br J Nutr 98: Suppl 1: 121–126.

    Google Scholar 

  8. 8

    Bastard JP, Maachi M, Lagathu C, et al, 2006 Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokkine Netw 17: 4–12.

    CAS  Google Scholar 

  9. 9

    Wellen KE, Hotamisligil GS, 2005 Inflammation, stress, and diabetes. J Clin Invest 115: 1111–1119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Spyridopoulos TN, Petridou ET, Skalkidou A, et al, 2007 Adiponectin levels are associated with renal carcinoma: A case-control study. Int J Cancer 120: 1573- 1578.

    Article  CAS  Google Scholar 

  11. 11

    Spyridopoulos TN, Petridou ET, Dessypris N, et al, 2009 Inverse association of leptin levels with renal cell carcinoma: results from a case-control study. Hormones (Athens) 8: 39–46.

    Article  Google Scholar 

  12. 12

    Fleming ID, Cooper JS, Henson DE, et al, 1997 AJCC cancer staging manual, Philadelphia: Lippincot-Raven; pp, 231–232.

    Google Scholar 

  13. 13

    Medeiros LJ, Jones EC, Aizawa S, et al, 1997 Grading of renal cell carcinoma: workgroup no. 2. Union internationale contre le cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer 80: 990–991.

    CAS  Google Scholar 

  14. 14

    Storkel S, Eble JN, Adlakha K, et al, 1997 Classification of renal cell carcinoma: workgroup no. 1. Union internationale contre le cancer (UICC) and the American joint committee on cancer (AJCC). Cancer 80: 987–989.

    PubMed  CAS  Google Scholar 

  15. 15

    Kahn BB, Flier JS, 2000 Obesity and insulin resistance. J Clin Invest 106: 473–481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Pischon T, Lahmann PH, Boeing H, et al, 2006 Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 118: 728–738.

    Article  CAS  Google Scholar 

  17. 17

    Calle EE, Kaaks R, 2004 Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4: 579–591.

    Article  CAS  Google Scholar 

  18. 18

    Wolk A, Mantzoros CS, Andersson SO, et al, 1998 Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst 90: 911–915.

    Article  CAS  Google Scholar 

  19. 19

    Hankinson SE, Willett WC, Colditz GA, et al, 1998 Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351: 1393–1396.

    Article  CAS  Google Scholar 

  20. 20

    Ma J, Pollak MN, Giovannucci E, et al, 1999 Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 91: 620–625.

    Article  CAS  Google Scholar 

  21. 21

    Yu H, Spitz MR, Mistry J, Gu J, Hong WK, Wu X, 1999 Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control study. J Natl Cancer Inst 91: 151–156.

    Article  CAS  Google Scholar 

  22. 22

    Petridou E, Dessypris N, Spanos E, et al, 1999 Insulinlike growth factor-I and binding protein-3 in relation to childhood leukaemia. Int J Cancer 80: 494–496.

    Article  CAS  Google Scholar 

  23. 23

    Giovannucci E, 2007 Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr 86: s836–842.

    Article  Google Scholar 

  24. 24

    Petridou ET, Sergentanis TN, Antonopoulos CN, et al, 2011 Insulin resistance: an independent risk factor for lung cancer? Metabolism 60: 1100–1106.

    Article  CAS  Google Scholar 

  25. 25

    Antoniadis Α, Petridou ET, Antonopoulos CN, et al, 2011 Insulin in relation to melanoma risk. Melanoma Res (Epub ahead of print).

  26. 26

    Baratta R, Amato S, Patane G, et al, 2003 Adiponectin and leptin: relationship with the insulin resistance syndrome. Diabetes 52: A81.

    Google Scholar 

  27. 27

    Major JM, Pollak MN, Snyder K, Virtamo J, Albanes D, 2010 Insulin-like growth factors and risk of kidney cancer in men. Br J Cancer 103: 132–135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Yuen JS, Akkaya E, Wang Y, et al, 2009 Validation of the type 1 insulin-like growth factor receptor as a therapeutic target in renal cancer. Mol Cancer Ther 8: 1448–1459.

    Article  CAS  Google Scholar 

  29. 29

    Parker A, Cheville JC, Lohse C, Cerhan JR, Blute ML, 2003 Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma. J Urol 170: 420–424.

    Article  CAS  Google Scholar 

  30. 30

    Ahmad N, Keehn CA, Coppola D, 2004 The expression of insulin-like growth factor-I receptor correlates with Fuhrman grading of renal cell carcinomas. Hum Pathol 35: 1132–1136.

    Article  CAS  Google Scholar 

  31. 31

    Sichani MM, Yazdi FS, Moghaddam NA, et al, 2010 Prognostic value of insulin-like growth factor-I receptor expression in renal cell carcinoma. Saudi J Kidney Dis Transpl 21: 69–74.

    PubMed  Google Scholar 

  32. 32

    Blüher S, Mantzoros CS, 2009 Leptin in humans: lessons from translational research. Am J Clin Nutr 89: Suppl: 991–997.

    Article  CAS  Google Scholar 

  33. 33

    Lichnovska R, Gwozdziewiczova S, Chlup R, Hřebiček J, 2005 Serum leptin in the development of insulin resistance and other disorders in the metabolic syndrome. Biomed Papers 149: 119–126.

    Article  CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Eleni Th. Petridou MD, MPH.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Spyridopoulos, T.N., Dessypris, N., Antoniadis, A.G. et al. Insulin resistance and risk of renal cell cancer: a case-control study. Hormones 11, 308–315 (2012).

Download citation

Key words

  • Renal Cell Carcinoma
  • Obesity
  • Insulin resistance
  • Leptin
  • Adiponectin