Risk Factors for Renal Cell Carcinoma

Currently, the only widely accepted risk factors for RCC are cigarette smoking and obesity. Each of these factors is believed to roughly double a person’s risk of developing RCC. Moreover, recent estimates from the American Cancer Society suggest that smoking and obesity account for nearly one-half of all the RCCs diagnosed in the U.S. This impressive statistic immediately raises two very important questions:

  1. How do smoking and obesity act inside the body to increase the risk of RCC? (i.e. what are the actual molecular mechanisms?) and
  2. What other unknown risk factors account for the remaining 50% of RCCs that occur in the U.S.?

A primary focus of our research program is to design epidemiological investigations to address each of the abovementioned questions regarding the etiology of RCC. For example, we have studies currently underway to address the potential that cigarette smoking is linked to RCC development through specific mutations of the von Hippel-Lindau (VHL) tumor suppressor gene. Along the same lines, we are also testing the hypothesis that obesity increases the risk of RCC through actions on the insulin-like growth factor I (IGF-I) and its cell-surface receptor. By employing epidemiological studies to improve our understanding of the actual mechanisms that link smoking and obesity to the development of RCC, we have the potential to inform on new strategies to prevent and treat RCC.

In addition to studying the biological mechanisms linking known risk factors with RCC development, we are also conducting investigations to illuminate new risk factors associated with the development of RCC. For example, we recently published findings suggesting that moderate alcohol consumption offers protection against RCC development in females but not males. We have also recently published an article showing that a history of urinary tract infections doubles a person’s risk of developing RCC regardless of their smoking or obesity history. Interestingly, the risk associated with history of urinary tract infections was considerably stronger among the subset of individuals who reported that they had smoked cigarettes. By illuminating new factors that are associated with development of RCC, we will be able to improve our understanding of how and why this cancer occurs and therefore be able to inform on new strategies to prevent the disease before it happens.