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Aspirin Decreases Genetic Mutations Associated With Inherited Colon Cancer

A new study suggests that aspirin will be a useful chemopreventative for Hereditary Colon Cancer patients. Aspirin may prevent the development of a particular type of common hereditary colorectal cancer in those at high risk for the disease.

Scientists at Jefferson Medical College believe they've uncovered a molecular mechanism by which aspirin interferes with colorectal cancer development in those individuals who carry particular gene mutations that makes them very likely to get the disease.

"Aspirin is a well known prophylaxis for cancer," says molecular geneticist Richard Fishel, Ph.D., professor of microbiology and immunology at the Kimmel Cancer Center of Thomas Jefferson University in Philadelphia, who with Josef Rschoff, M.D., of the University of Regensburg, Germany, led the research. "The new twist is that aspirin suppresses the accumulation of mutations that are the cause of a common inherited cancer." Similar mutations are found in 5-10% of sporadic colorectal, endometrial and ovarian cancers.

Their work appears September 15 in the Proceedings of the National Academy of Sciences.

Drs. Fishel, Rschoff and their colleagues examined human colon cancer cell lines with defective mismatch repair genes, which are necessary to fix normal cell damage that occurs when cells divide and multiply. These mismatch repair genes were discovered by Dr. Fishel and Dr. Richard Kolodner (now at the Ludwig Institute for Cancer Research in San Diego) in 1993 to be the cause of the most common form of hereditary cancer known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC).

The scientists then treated the colon tumor cells with two drugs: aspirin and sulindac, which are both nonsteroidal anti-inflammatory drugs and known cancer preventatives. They found that the drugs largely suppressed the genetic instability that underlies the development of cancer in HNPCC.

"Our results appear to suggest a very simple
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Contact: Steve Benowitz
steven.benowitz@mail.tju.edu
(215) 955-6300
Thomas Jefferson University
14-Sep-1998


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