Friday, April 4, 2014

Renal Cell Carcinoma: Risk Factors and Epidemiology

Renal cell carcinoma (RCC) is the most common kidney tumor worldwide. Many patients are curious as to why they have a tumor and if there is anything they did to cause it? There are not many, well-established risk factors for RCC.  We will discuss what is known below.

RCC Epidemiology Facts

RCC is more common in the developed, rather than the developing world as the incidence increases with age and other age-related risk factors.

  • Countries of Northern America, Europe, Australia and New Zealand have the highest risk of RCC in the world.
  • Countries with the lowest-risk of RCC are in Africa and the Caribbean. [1]  
  • In the US, there are approximately 64,000 new cases of renal cancer per year and 13,500 people die of renal cancer each  year.  
    • The incidence of renal cancer has steadily risen over the past few decades due to the increased use of axial imaging. 
    • This corresponds to a steady increase in localized cancers while the rates of locally-advanced and metastatic disease have remained stable. [2]  
    • Interestingly, despite the steady increase in the number of cancers, the mortality from kidney cancer has remained stable.

RCC Risk Factors

RCC is more common in men than women.  It is the 6th most common cancer in men and the 8th most common cancer in women.  The other well-established risk factors that will be discussed in this blog include tobacco exposure and obesity.  Putative risk-factors for RCC are listed below and will not be discussed in this blog as there is neither strong evidence in favor of or against each risk.  In addition, there are a number of genetic causes of RCC.  While these genetic causes are strong predictors of RCC, they are rare and will be the focus of a later blog.  

Well-Established Risk Factors for RCC

Tobacco Exposure
Genetic Causes

Possible Risk-Factors for RCC

Chemical Exposures (lead compounds, aromatic hydrocarbons)
Occupational Exposures (asbestos)
Radiation Therapy
Dietary Factors (high fat, low fruit/vegetables)

Tobacco Exposure and Renal Cell Carcinoma

Cigarette smoking is the most well-established risk factor for RCC.  It is believed that chronic smoking leads to DNA damage through chronic tissue hypoxia. The risk of RCC is proportional to the dose and duration of exposure.  A meta-analysis of 24 studies demonstrated a 38% increased risk of RCC with any smoking exposure; that risk was modified by male sex and more cigarette exposure on a daily basis.  This study also demonstrated that smoking cessation alleviates the risk of RCC, but only 10 years after quitting.[3]
Hunt et al. Int J Cancer, 2005.

Not only has smoking been attributed to an increased risk of RCC, but smokers also have a higher risk of death from RCC.  In fact, it has been demonstrated that for every pack-year of smoking history a patient has a 1% increased risk of death from RCC.[4]

Obesity and Renal Cell Carcinoma

Rates of RCC increase with increasing Body Mass Index.  In 11 studies comparing RCC and BMI, each 5kg/m3 increase in BMI corresponds to a 25% increase in the rate of RCC in men, and 34% increase in women.[5]  Obesity leads to an altered endocrine milieu, led by compensatory hyperinsulinemia and production of adipokines, which creates an environment of inflammation and oxidative stress leading to the formation of RCC.[6]

Renehan et al. Lancet, 2008.

Contrary to the relationship with smoking, obese patients with RCC have an improved long-term survival after diagnosis.[7]  This has been termed the "obesity paradox" and exists in a number of other disease states like patients with chronic kidney disease on dialysis, diabetes and heart failure.  Recent evidence indicates that obese patients may present with smaller, earlier-stage and lower grade tumors - indicating for the relative improvement in survival.[8]


  • Renal cell carcinoma is more common in the developed world than developing nations.
  • The incidence of RCC has increased dramatically in the US - this corresponds to an increased use of axial imaging.
  • The number of deaths from RCC has remained stable over the same time period, reflecting the stable rates of advanced and metastatic disease.
  • Risk factors for RCC include:
    • Male Sex: men are more likely than women to develop RCC
    • Smoking: 
      • The risk of RCC increases with increasing exposure to tobacco smoke.
      • The risk of death from RCC also increases with tobacco exposure.
    • Obesity:
      • The risk of RCC increases with increasing BMI.
      • The risk of death from RCC is lower in patients with a larger BMI (this is termed the "obesity paradox").

This blog was written by Michael Gorin, MD, resident at the Brady Urological Institute at Johns Hopkins.  Visit the Brady Urological Website for more information on kidney cancer and its treatment.

[1] Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, Kiemeney LA. The epidemiology of renal cell carcinoma.Eur Urol. 2011 Oct;60(4):615-21. doi: 10.1016/j.eururo.2011.06.049. Epub 2011 Jul 5.
[2] Chow WH, Dong LM, Devesa SS.  Epidemiology and risk factors for kidney cancer.
Nat Rev Urol. 2010 May;7(5):245-57.
[3] Hunt JD, van der Hel OL, McMillan GP, Boffetta P, Brennan P.Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies.  Int J Cancer. 2005 Mar 10;114(1):101-8.
[4] Kroeger N, Klatte T, Birkhäuser FD, Rampersaud EN, Seligson DB, Zomorodian N, Kabbinavar FF, Belldegrun AS, Pantuck AJ.  Smoking negatively impacts renal cell carcinoma overall and cancer-specific survival.  Cancer. 2012 Apr 1;118(7):1795-802. doi: 10.1002/cncr.26453. Epub 2011 Aug 25.
[5]  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.Lancet. 2008 Feb 16;371(9612):569-78.
[6] Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2010;61:301–316.
[7] Choi Y, Park B, Jeong BC, et al. Body mass index and survival in patients with renal cell carcinoma: a clinical-based cohort and meta-analysis. Int J Cancer. 2013;132(3):625–634.
[8] Hakimi AA1, Furberg H, Zabor EC, Jacobsen A, Schultz N, Ciriello G, Mikklineni N, Fiegoli B, Kim PH, Voss MH, Shen H, Laird PW, Sander C, Reuter VE, Motzer RJ, Hsieh JJ, Russo P.  An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma.J Natl Cancer Inst. 2013 Dec 18;105(24):1862-70. doi: 10.1093/jnci/djt310. Epub 2013 Nov 27.

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