New Hereditary Cancer Mutation Found

Lost gene may be responsible for colon, endometrium, ovary cases

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Albert de la Chapelle, MD, PhD (Ohio State University)

Scientists have combined genetic testing with genealogical detective work to discover and trace the source of an unusual gene mutation. That mutation apparently was brought to the United States at least 13 generations ago and may be responsible for a sizeable portion of certain hereditary cancers in Americans.

People with this mutation are at high risk for developing cancer of the colon, endometrium and ovaries. The condition is known as hereditary nonpolyposis colon cancer (HNPCC).

The study represents a collaboration among researchers at Creighton University Medical Center, Omaha, Neb., the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, and Leiden University and Erasmus University Medical Center, both in the Netherlands. The findings are published in a recent issue of the Journal of the American Medical Association.

"Our challenge now is to determine how common this mutation is in the United States," says Albert de la Chapelle, MD, PhD, co-director of the OSU Comprehensive Cancer Center's Molecular Biology and Cancer Genetics Program and a co-author of the paper. "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."

So far, the scientists have identified 566 individuals in nine families who are descendents of that one early immigrant. Of these, 137 have undergone genetic counseling and testing. The tests showed that 44.5 percent (61 of the 137) carry the genetic mutation and should therefore receive regular check-ups for colorectal, endometrial and ovarian cancer.

The new mutation is known as a deletion mutation, in which part of the gene known as MSH2 is lost.

The discovery of the new mutations should improve the detection of HNPCC, which is usually diagnosed based on a person's family history or the presence of certain gene mutations in one of five genes, or both.

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. Furthermore, these tests usually do not detect deletion mutations. The new test for the deletion mutation is less expensive than the usual HNPCC genetic tests.

Collected evidence allowed the researchers to conclude that the mutation was in either the husband or wife of a couple that had immigrated from Germany and settled in Pennsylvania in 1727. The couple had 11 children.

The researchers believe there are family members with this mutation throughout the United States, and that most would not know that they had descended from the original German couple.

People with cancers of the colon, rectum, endometrium and ovaries or who have a family history of these cancers, should consider seeking a consult with a local genetics counselor to determine if they should be tested for the new mutation.

For more information, call 800-293-5123 or visit www.medicalcenter.osu.edu.

— Ohio State University Medical Center