Researchers identify individuals at risk for developing colon cancer

July 13, 2009

A new study identifies a group of individuals at increased risk for developing colon cancer and holds the promise for developing new tailored cancer treatments. The study in this week's issue of the Proceedings of the National Academy of Sciences (PNAS) is by Sanford Markowitz, M.D., Ph.D., the Markowitz-Ingalls Professor of Cancer Genetics at Case Western Reserve University School of Medicine and oncologist at the Ireland Cancer Center of University Hospitals Case Medical Center, and colleagues.

"The bottom line is that we have found an uncommon but potentially important group of individuals who are born with certain genetic mutations and are at increased risk for developing colon cancer," says Dr. Markowitz, who is also an investigator in the Howard Hughes Medical Institute. "This is yet another step towards identifying who is at increased risk for this deadly form of cancer and it may potentially allow us a greater ability to detect and treat, as well as develop therapies, for cancer."

Dr. Kishore Guda, a postdoctoral fellow in Dr. Markowitz's laboratory, is lead author on the study. Dr. Markowitz's laboratory along with colleagues at Johns Hopkins Medical Center analyzed DNA from individuals who are born with mutations that cause defects in the pathways that put sugar groups on proteins. The normal process, called glycosylation, is used to synthesize mucus and is involved in many cellular activities. The individuals with this genetic defect appeared to develop colon cancer later in life. Data was from patients at UH Case Medical Center and Johns Hopkins.

A defect in glycosylation is a hallmark of many cancers, but the reason for this defect has been unknown. This study discovered the presence of mutations in a group of enzymes, called GALNTs, which are required for normal glycoslylation. These mutations contribute to alterations in the glycosylation process, and in turn, to the development of colon cancer.

"Our findings support the idea that defects in glycosylation, the process for making mucus, can contribute to tumor development," said Dr. Markowitz. "Knowing how these glycosylation enzymes malfunction and contribute to tumor formation may give us another target that can be potentially used to prevent the development of colon and other cancers. Certainly, individuals who have these mutations should be getting screening for colon cancer, so that the disease can be caught during the early stages when it is highly curable."

Colon cancer, the second leading cause of cancer deaths in the U.S., accounts for 50,000 deaths annually.
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About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Eleven Nobel Laureates have been affiliated with the school.

Annually, the School of Medicine trains more than 770 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News and World Report "Guide to Graduate Education."

The School of Medicine's primary clinical affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu.

About University Hospitals

University Hospitals serves the needs of patients through an integrated network of hospitals, outpatient centers and primary care physicians. At the core of our health system is University Hospitals Case Medical Center. The primary affiliate of Case Western Reserve University School of Medicine, University Hospitals Case Medical Center is home to some of the most prestigious clinical and research centers of excellence in the nation and the world, including cancer, pediatrics, women's health, orthopedics and spine, radiology and radiation oncology, neurosurgery and neuroscience, cardiology and cardiovascular surgery, organ transplantation and human genetics. Its main campus includes the internationally celebrated UH Rainbow Babies & Children's Hospital, ranked among the top hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Ireland Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. For more information, go to www.uhhospitals.org

University Hospitals Case Medical Center

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