Programs recipients

The Cancer Research Foundation Program in GI Cancer Prevention And Control

Principal Investigator: Nathan Ellis   ·   University of Chicago

In 2005, the CRF made a $1.5 Million grant to the University of Chicago Cancer Research Center (UCCRC) to launch the Cancer Research Foundation Program in Gastrointestinal (GI) Cancer to aid in the building of a comprehensive cancer program, leading efforts in population-based research, genetic risk assessment, computational biology, cancer prevention, detection and treatment. This grant has helped build infrastructure for the GI Program; expand the GI Program model into other cancer areas; and obtain comprehensive status from the National Cancer Institute.

In 2004, 256,000 new cases of colon, rectal and upper gastrointestinal (esophageal, stomach, liver and pancreatic) cancer were diagnosed, resulting in 135,000 deaths. With clinical and laboratory expertise in gastroenterology, oncology, advanced imaging, radiation oncology and surgical oncology, the University of Chicago Cancer Center is well-positioned to play a leadership role in identifying better screening and treatment methods for these diverse and devastating diseases.

It is well-established that individuals with IBD are pre-disposed to developing colorectal cancer; however, the basis for this increased risk is unknown. With our existing strengths in cancer genetics and risk assessment, IBD, and GI cancer screening, the University has the intellectual and clinical infrastructure to make significant inroads in the understanding of the genetic and environmental factors that predispose individuals to colorectal carcinoma. Our program will focus on the genetics of colorectal carcinoma in high-risk families.

The major focus of Dr. Ellis' research is in the genetic epidemiology of cancer susceptibility genes, specifically, the identification of novel breast cancer-and colon cancer-causing genes. These efforts are divided into two categories candidate gene studies and genome-wide association studies. Dr. Ellis's research will expand not only our efforts in GI tumors, but also our programs in population sciences and women's cancers.

Dr. Ellis has developed a powerful new approach to identify low-penetrance alleles (genes which

confer a low, but distinct, risk of cancer) based on his hypothesis that low-penetrance genes will

be detectable in high-risk colorectal carcinoma cases. Dr. Ellis has demonstrated the validity of

this hypothesis by pilot proof-of-principle studies in patients with colorectal carcinoma. For

future association studies, he has assembled collections of colon cancer and breast cancer patients in New York and equivalent numbers of population-matched controls. Samples are

available from over 1500 Ashkenazi Jewish colon cancer patients and over 2000 Ashkenazi Jewish breast cancer patients (the Ashkenazi Jewish population has been remarkably progressive

and proactive in participating in research that will identify disease risk and improve the health of individuals). In addition, for screening purposes, he has available collections of > 100 high-risk

cases with strong family histories of colon or breast cancer in whom mutations in the relevant known cancer genes have been excluded. Together with the unique population of IBD patients assembled by researchers in our GI Section, Dr. Ellis will have patient resources unparalleled in

the world, with the power to detect factors that cause an increased relative risk of approximately

1.5 for alleles with frequencies greater than 0.025%.

For genome-wide association studies (i.e., finding unknown genes in our genome that predispose to cancer), Dr. Ellis has hypothesized that a selection of patients from high-risk families in a founder population-the Ashkenazi Jewish population-will increase the power and efficiency of such studies, and he has demonstrated the power of this approach in a series of 57 BRCA negative breast cancer cases from families with four or more breast cancers. The identification of new cancer susceptibility alleles will allow us to identify the most susceptible people in a population, and provide them with options to pursue earlier and more frequent cancer surveillance, chemopreventive treatments, and risk-reducing surgeries.