May 20, 1998 IOWA CITY, Iowa -- A gene causing familial juvenile polyposis (FJP), a disorder that causes the growth of polyps in the colon or upper gastrointestinal tract, has been identified.
Dr. James Howe, University of Iowa assistant professor of surgery, led an international team that identified a mutated tumor suppressor gene found in families with the disorder from Iowa, Mississippi, Finland and England. The finding is published in the May 15 issue of the journal Science. FJP affects about 1 in 100,000 people, Howe says -- usually with the onset of symptoms within the first two decades of life. The most common symptom is rectal bleeding.
The condition was at first thought to be benign, however, in a 1975 study, University of Iowa College of Medicine researchers demonstrated that people with FJP had a high risk of developing gastrointestinal cancer. If an individual has a parent or sibling with FJP, they have a 50 percent chance of also having the disease plus an increased risk of cancer.
While identification of a gene responsible for FJP will help to identify carriers of the abnormal gene and facilitate the screening of family members, the implications of this finding may reach beyond FJP.
"FJP is a relatively rare disease. However, 75 percent of colon cancer cases have chromosomal losses from this region of the genome," Howe says. "Understanding this gene may increase our understanding of colorectal cancer in general, and could provide insights into its diagnosis and treatment."
It took less than two years for Howe and his colleagues to pinpoint the errant gene. Howe credits the Human Genome Project for acceleration the process of gene identification, particularly for making available good markers to help determine the chromosome where genes are located. The group was able to identify the chromosome using linkage studies a year after beginning the project. The gene, SMAD4/DPC4, was originally identified and mapped in 1996 by researchers at Johns Hopkins University. Deletions of this gene have been described in 50 percent of pancreatic cancers and in 15 percent of colorectal cancers. Howe's research is a work in progress.
"We know that this gene causes FJP in a subset of families, but we also know that it doesn't cause it in all families," Howe says. "The incidence may be as low as 20 percent or as high as 55 percent. There are clearly other genes which may cause FJP."
The next phase of this study is to determine if SMAD4/DPC4 is mutated in members of different families and to look at other genes related to SMAD4/DPC4 to determine whether mutations in those genes produce similar disorders.
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