Colorectal cancer ranks second only to lung cancer as the leading cause of cancer-related death among men and women in the United States. Some people inherit a genetic susceptibility, but for well over 80 percent of people who develop the disease, diet strongly influences whether colorectal cancer will occur and whether it will progress.

The National Institutes of Health has awarded Leonard Augenlicht, Ph.D., professor of medicine and of cell biology and director of the Albert Einstein Cancer Center’s Biology of Colon Cancer Program, three new grants totaling $7.1 million to further study how diet influences colon cancer.

Researchers know that intestinal stem cells—vital for maintaining intestinal tissue—can undergo malignant transformations leading to colon cancer. In previous studies, Dr. Augenlicht showed that feeding mice a high-fat, low-fiber, Western-style diet profoundly alters the differentiation of intestinal stem cells and their energy metabolism. He has hypothesized that these and other diet-induced changes can turn certain stem cells into cancer stem cells.

With two five-year grants of $2.5 million and $1.5 million, Dr. Augenlicht will study how feeding mice the higher-risk, Western-style diet influences the function of different kinds of intestinal stem cells. This research may identify markers for detecting elevated cancer risk and the underlying mechanisms that lead to tumor development.

The third grant, for $3.1 million over five years, will allow co-principal investigators Dr. Augenlicht and Winfried Edelmann, Ph.D., and co-investigator Matthew Gamble, Ph.D., to study colorectal cancer associated with Lynch syndrome (also called hereditary nonpolyposis colorectal cancer). Dr. Edelmann is a professor of cell biology and of genetics and the Joseph and Gertrud Buchler Chair in Transgenic Medicine, and Dr. Gamble is an associate professor of molecular pharmacology and of cell biology.

Lynch syndrome occurs because people inherit mutations in one of their two copies of MSH2 or other genes in the mismatched-DNA repair pathway—a key pathway for fixing DNA replication errors. People with Lynch syndrome (about 150,000 Americans) have up to an 80 percent risk of developing colorectal cancer during their lifetimes.

Dr. Edelmann has developed a new mouse model of Lynch syndrome that mimics the genetic and dietary influences of the human disease. Drs. Edelmann and Augenlicht found that feeding the animals a Western-style, higher-risk diet strongly promotes tumor development in the colon, just as it does in humans.

With the new grant, Drs. Augenlicht, Edelmann, and Gamble will study genetic and dietary interactions in this Lynch syndrome mouse model. These findings could lead to advances in detecting, preventing, and treating Lynch syndrome in particular and colorectal cancer in general.