From Our 2008 Archives

Colon Cancer Gene Traced to Arrival in United States

By Amanda Gardner
HealthDay Reporter

WEDNESDAY, Jan. 2 (HealthDay News) -- Mr. and Mrs. George Fry sailed from the Old World to the New World around 1630 on a ship most likely named the William & Mary.

Along with at least two of their four children, they most certainly brought with them a unique genetic mutation for colon cancer, a new study shows.

This "founder mutation," which increases the risk for colon cancer, has now been passed on to a considerable number of the descendants of the original couple, the University of Utah researchers added.

The mutation has not been found in England, said study author Deb Neklason, meaning that it likely originated with either Mr. or Mrs. Fry. Her report is published in the January issue of Clinical Gastroenterology and Hepatology.

"It is a neat story of a so-called founder mutation, that is one that from its origin in a single individual has multiplied in a given population . . . so that today, it is carried by members of ostensibly unrelated families who yet descend from the one founder," explained Dr. Albert de la Chapelle, distinguished university professor of the Human Cancer Genetics Program at Ohio State University's Comprehensive Cancer Center. "It is usually a matter of chance whether such a mutation becomes more and more widespread with time, or whether it disappears. This phenomenon is called genetic drift. In this case, the mutation appears to have spread but perhaps not excessively so."

The ACP gene mutation identified by Neklason and her colleagues causes attenuated familial adenomatous polyposis (AFAP), a condition which results in a 69 percent greater risk of developing colon cancer by the age of 80. This is compared to a roughly one in 24 chance for the general population.

Like colorectal cancer in general, cancer resulting from the ACP mutation can be prevented with appropriate screening. But the researchers say it's not easy to detect people with the mutation through normal check-ups.

De la Chapelle was one of a group of scientists who discovered a different founder mutation in 2004, this one in the MSH2 gene, that is also responsible for an increased risk of colorectal cancer. "[The MSH2 mutation] causes regular and other cancers typical of the Lynch syndrome, and the risk is very high, whereas the APC one causes a mild form of polyposis, which does have a relatively high cancer risk," de la Chapelle noted.

The MSH2 mutation was brought to Pennsylvania by a German immigrant couple in the early 18th century.

Neklason and her colleagues arrived at their discovery by studying two large families, one in Utah and one in New York, that carry the ACP mutation. The Utah family has more than 7,000 descendants in nine generations.

The researchers relied on family reports, the Utah Population Database, records maintained by the Church of Jesus Christ of Latter-day Saints (Mormons), as well as statewide cancer records in Utah and Idaho and Utah death certificates and birth certificates.

Family members underwent genetic analysis and colonoscopy data was available on 120 individuals within these families.

Both families were linked to the Fry family.

Because the couple came here so long ago, many more people than originally thought may carry the mutation. The researchers have identified 14 additional families in the United States who have the exact same mutation.

"They are almost certainly related. They all come off of this founder somewhere, but we don't know where, and we only have a glimpse," Neklason said. "We hope with this publication we're going to be able to find many families throughout the country that have the genetic change."

Current guidelines for detection of people with this mutation are murky and, Neklason estimated, may detect only about 87 percent of these people.

However, individuals can help their own cause.

"This stresses the importance of knowing your family history and your immediate family history," Neklason said. "The other big implication is that it's preventable, and that's the important part."

Current screening methods can detect precancerous polyps and remove them before they turn malignant.

SOURCES: Albert de la Chapelle, M.D., Ph.D., Distinguished University Professor, Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, Columbus; Deb Neklason, Ph.D., research assistant professor, Huntsman Cancer Institute, University of Utah, Salt Lake City; January 2008, Clinical Gastroenterology and Hepatology

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