Maria Czyzyk-Krzeska of the University of Cincinnati received a two-year, IDEA grant of $474,562 from the Department of Defense to work on the effects of tobacco smoke on growth of clear cell renal cell carcinoma (ccRCC).

Smoking is the major risk factor in getting kidney cancer, but the genetic signaling in RCC that is caused by smoking is little understood. The objective of the study is to determine the genetic mutations and other genetic sequencing issues that are related to heavy smoking adults by collecting and comparing RCC tissue samples from heavy smoking military veterans to men with RCC who have never smoked. In subsequent phases of her research, Dr. Czyzyk-Krzeska will analyze the genetic disparities between the two populations with the intention that this analysis will lead to new mechanisms of diagnosis and treatment of ccRCC in the heavy smoking population both in veterans and the general population.

Based on a study of 200,000 veterans over a 26-year period, the male military population over the age of 40 has a five to six times increased incidence of RCC as compared to the general population. This fact may be due to the high prevalence of smoking in the military. Although 30% of military personnel smoke, the percentage skyrockets to nearly 75% of military veterans as being smokers or having smoked at some time during their lives as compared to less than half of the general population who never served in the military.

This disparity in kidney cancer incidence rates between military veterans and the general population informs ACKCs decision to seek funding from the Department of Defense for kidney cancer research.

In this study, Dr. Czyzyk-Krzeska will be partnering with the Veterans Administration in Cincinnati, a major VA center that services 17 counties in Ohio, Kentucky, and Indiana. The center treats kidney cancer patients and will provide the RCC tissue samples to Dr. Czyzyk-Krzeska.

This is the second grant that Dr. Czyzyk-Krzeska has won from the DoD cancer research program. In FY2006, she was awarded $932,900 to study the genetic causation of RCC. This first DoD grant allowed Czyzyk-Krzeska to concentrate her work on clear cell renal cell carcinoma so to build the necessary infrastructure to do the genetic research on RCC, specifically, collecting a bank of human matched tumor/kidney tissue specimens and analyzing expression of tumor suppressors in these samples. This early work led to the discovery of microRNA-204, a tumor suppressor that is uniformly lost in kidney cancer and to the identification of TRPM3, a gene that has an oncogenic function in renal cancer and which can be inhibited by small molecules, thus representing an actionable target.