Investigating the role of aging and poor nutrition on colon cancer

Two risk factors – getting older and eating poorly – are implicated in more than 80 percent of colon cancer cases in developed countries. Now, researchers at Albert Einstein College of Medicine of Yeshiva University have received a $3.2 million grant from the National Institutes of Health (NIH) to investigate how aging and poor nutrition interact to cause the mutations responsible for driving colon cancer development.

Colon cancer is the second leading cause of cancer-related deaths in the United States (behind lung cancer) and the third most common cause of cancer in men and women. According to the Centers for Disease Control and Prevention, more than 130,000 people are diagnosed with the disease each year and more than 50,000 men and women will die from it. The vast majority of these cancers occur in people 50 or older.

"We know that age is a major risk factor for all types of cancer, and we also understand that lifelong dietary habits play an extremely important role in the development of colorectal cancers," said Leonard Augenlicht, Ph.D., professor of medicine and of cell biology at Einstein, director of the Biology of Colon Cancer Program at the NCI-designated Albert Einstein Cancer Center, and principal investigator on the grant.

Dr. Augenlicht has used mouse models to replicate how a Western-style diet affects the colon. Such diets are high in fat and low in levels of vitamin D, calcium and fiber. Not only did the diet cause a notable increase in the incidence of sporadic colon cancer in mice, but Dr. Augenlicht also saw ominous changes at the cellular level well before tumors developed.

Those changes were observed within intestinal crypts – glands embedded in the wall of the small intestine. The crypts give rise to cells that absorb nutrients and that protect it from harmful substances, including the bacteria residing in the intestine. The crypts also house stem cells, which make daughter cells that travel from the crypts to repopulate and restore the intestine's mucosal lining.

Dr. Augenlicht's lab recently found that when mice are fed a Westernized diet, the crypts undergo an inflammatory response that seems to cause their stem cells to accumulate mutations. In addition, the daughter cells of these stem cells tend to stay within the crypt rather than travel into other portions of the intestinal lining – which may be a sign that stem-cell mutations were accumulating in them. Aging is also implicated in mutations, so the combination of a Westernized diet and getting older would increase the probability of colon tumors arising from mutated intestinal cells.

The Einstein researchers will use several novel techniques to find how age and diet interact to produce the intestinal stem-cell mutations that appear to be key players in causing colon cancer. One of those techniques was developed by Jan Vijg, Ph.D, professor and chair of genetics, professor of ophthalmology & visual sciences, and the Lola and Saul Kramer Chair in Molecular Genetics at Einstein and a key co-investigator on the renewed grant. Known as single-cell whole-genome sequencing, this technique will determine both the quantity and types of mutations that affect stem cells of the intestinal crypts.

"Our aim is to better understand how tumors develop and to come up with new approaches for preventing colon cancer and detecting it early," said Dr. Augenlicht.

Provided by Albert Einstein College of Medicine