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International Team Identifies Deletion Linked With High Multiple-Cancer Risk


An international team of researchers claim to have identified and genealogically traced a rare deletion mutation linked to hereditary nonpolyposis colon cancer. The mutation predisposes individuals to cancers of the colon, endometrium, and ovaries.

The team said that the deletion in the MSH2 gene “apparently” came to the United States more than 250 years ago, “and it may be responsible for a sizeable portion of certain hereditary cancers in Americans.”

“Our challenge now is to determine how common this mutation is in the United States,” Albert de la Chapelle, co-director of the OSU Comprehensive Cancer Center’s Molecular Biology and Cancer Genetics Program and a co-author of the paper, said in a statement. “The good news is we have a simple way of detecting it, and we are now devising strategies to comb the nation for this mutation.”

To date, de la Chapelle and colleagues have identified 566 individuals in nine US families descended from the German immigrant believed to have introduced the mutation into the country. The families reside in North Carolina, Kentucky, Tennessee, Missouri, Iowa, Nebraska, Texas, Utah, and California.

Of the 566 individuals, 137 had undergone testing for the mutation, and 44.5 percent, or 61 individuals, were found to carry the deletion. The discovery promted researchers to urge the people to “receive regular check-ups for colorectal, endometrial, and ovarian cancer.”

Individuals are usually diagnosed with HNPCC based on family history or the presence of certain mutations in one of five genes, or both, according to the scientists. However, most people with a family history of the disease do not have an easily detectable mutation, and the genetic tests for mutations are expensive. Besides, existing tests “usually do not detect” genetic deletions. The new test for the deletion mutation is less expensive than the usual HNPCC genetic tests, the researchers reported.

“We hope that families who have already been tested and for whom no mutation was found will return for a genetic consult and be retested for this specific mutation,” Coronel said in the statement.

The deletion was initially discovered by a team from the Netherlands, Ohio State University, and Henry Lynch at Creighton Medical Center. De la Chapelle led this group, which went on to describe the HNPCC syndrome. Soon, members from these groups found families with the mutation, which led them to begin a genealogical study to trace the origin of the deletion.

In its Feb. 11 Journal of the American Medical Association report, the team was able to discern that the mutation made its way to Pennsylvania from Germany in 1727. It turned out that this individual — it was not known whether it was the mother or father — was a common ancestor of three of the nine families studied.

“Knowledge about this mutation will help us identify more high-risk individuals who need education about HNPCC and the steps they can take to protect themselves against the cancers associated with the syndrome,” Stephanie Coronel, genetic research associate at Creighton Medical Center and one of the paper’s co-authors, said in the statement.

Darrell Ward, a spokesman for Ohio State University, said a PCR-based test that detects the deletion currently exists, and that his school’s molecular pathology lab charges $200 for the procedure. Ward said that since the primers have been published, any lab with PCR technology can perform the test. He currently knows that Mayo Clinic in Rochester, Minn., charges $500 for a test that hunts for all deletions in the MSH2 gene, but that this test is less definitive.

— KL



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