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APC Gene Mutation May Not Lead To Increased Colon Cancer Risk in Ashkenazi Jews

Jan 1, 1998
Volume: 
12
Issue: 
1
  • Gastrointestinal Cancer, Ovarian Cancer, Colorectal Cancer

A genetic mutation in the adenomatous polyposis (APC) gene found in 7% of Ashkenazi Jewish families in the United States does not necessarily lead to colon cancer, according to a study in the December 15, 1997, issue of Cancer Research.

The study’s conclusion contrasts with another study published in the September 1997 issue of Nature Genetics. That study determined that the 6.1% of the Ashkenazi Jewish population who test positive for the altered APC gene are at increased risk of developing colon cancer during their lifetime.

Screening Ashkenazis for Mutation Called “Premature”

The new study, conducted at Fox Chase Cancer Center in Philadelphia, concluded that inheritance of a mutation in the APC gene alone does not increase colon cancer risk and suggested that screening this entire population for the flaw may be premature. In the absence of a significant family history of colon cancer, the study found that the APC gene alteration does not contribute to colon cancer.

Dr. Andrew Godwin, a Fox Chase molecular biologist and human geneticist, looked at 264 individuals in 158 Ashkenazi Jewish families with a family history of breast and/or ovarian cancer. In contrast, the previous study, led by Dr. Bert Vogelstein of the Johns Hopkins Oncology Center, tested Ashkenazi Jews with a family history of colon cancer.

“We chose to study families genetically predisposed to breast and/or ovarian cancer since they also have been known to be four times more likely than the general public to develop colon cancer,” said Godwin. “However, we determined their increased incidence of colon cancer was not linked to this specific alteration in the APC gene.”

Godwin found that, of the 158 families studied, 42 reported having at least one family member with colorectal cancer, yet none of these 42 families tested positive for the APC mutation. Conversely, none of the 12 individuals who tested positive for the mutation had developed colorectal cancer nor had any of their relatives.

Other Factors May Be Important Godwin’s results indicate that factors other than the mutated APC gene may be at work. “The next step would be to conduct studies comparing the clinical aspects of colon tumors from Jewish patients who tested positive for the specific APC mutation with those who had tested negative,” said Godwin.

The APC gene functions as a tumor suppressor, and mutations in this gene are believed to contribute to the development of colorectal cancer. The premise of the Nature Genetics study was that this specific alteration may be more susceptible to disease-causing mutations. Godwin’s results suggest that, in the absence of other inherited factors, this slight alteration alone does not appear to affect the body’s normal function of protecting itself from cancer.

Dr. Carlo M. Croce, Editor of Cancer Research, applauded the study’s findings. “It is very important for people to know their risk of developing cancer, when it is possible,” he commented. “At the same time, people should know when not to worry. We are pleased to publish information that may help Ashkenazi Jews and their physicians to make more reasoned decisions about genetic screening for the 11307K mutation.” 

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