May 8, 2014 - (BRONX, NY) - 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.
The research will be funded by grant R01CA174432 from the National Cancer Institute, part of the NIH.
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2013-2014 academic year, Einstein is home to 734 M.D. students, 236 Ph.D. students, 106 students in the combined M.D./Ph.D. program, and 353 postdoctoral research fellows. The College of Medicine has more than 2,000 full-time faculty members located on the main campus and at its clinical affiliates. In 2013, Einstein received more than $155 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center -Einstein's founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States. For more information, please visit www.einstein.yu.edu, read our blog, follow us on Twitter, like us on Facebook, and view us on YouTube."