TUESDAY, Feb. 10, 2004 (HealthDayNews) -- It's a medical detective story that starts with the emigration of a married couple from Germany to Pennsylvania in the early 1700s and ends with implications for today's programs to screen for the risk of colorectal cancer.
The couple had 11 children, a typically large family for that era. Those children married and had families of their own, until their descendants numbered in the thousands, a new study reports.
And over the decades and centuries, an unexpectedly large number of those descendants were diagnosed with cancer. Most were cancers of the colon and rectum, but there also were other tumors such as endometrial cancer and ovarian cancer among the women.
It wasn't until recently that researchers, armed with the tools of modern genetics, were able to establish the link. The original German immigrants brought with them a mutation of a gene designated MSH2, a mutation that predisposes people to develop some cancers, particularly colorectal cancer.
The mutation appears to have originated with one of the married pair. Each of their children had a 50-50 chance of inheriting what is called the "founder mutation," and each person with that mutation had a 50 percent chance of passing it on to a child.
The existence of the mutation was first noticed in 1997 by Riccardo Frodde, a geneticist then at Leiden University in the Netherlands, who found evidence of it in more than 50 families there.
The story then moved to the United States, where a group of researchers headed by Dr. Henry T. Lynch, a professor of preventive medicine at the Creighton University School of Medicine in Nebraska, found the same mutation in members of seven apparently unrelated families with a history of colorectal cancer.
That discovery indicated the families might, in fact, be related, says Stephanie M. Coronel, a genetic research assistant in Lynch's laboratory.
"That is how we started doing genealogical work, looking at different sites on the Web," Coronel says.
Those studies pointed toward a common origin of the mutation, and they drew in another researcher, Dr. Albert de la Chapelle, a professor of cancer genetics at Ohio State University. He had found the same mutation in two other families.
"It was pure coincidence that Dr. Lynch and I, who knew each other, identified the same mutation in some of his patients and some of my patients," de la Chapelle says. "It was not very difficult to start putting two and two together."
The result, reported in the Feb. 11 issue of the Journal of the American Medical Association, was detection of the founder mutation in 61 members of the nine families in admittedly partial testing; only 137 of 566 members of the families have been tested.
"We have shown by now that four of the nine families descended from the founder couple, and we are almost 100 percent certain that all do," de la Chapelle says.
This is a big surprise, he says, because founder mutations traditionally have been seen only in relatively small, isolated populations, such as Icelanders and Ashkenazi Jews.
"You do not expect to see it in a mixed population, such as we have in the United States," de la Chapelle says.
The implications of the discovery may extend to many Americans outside the tested families, Coronel says, since it is estimated that 10 percent of all colorectal cancers are hereditary. The presence of colorectal cancer in a family can indicate a need for genetic testing, she says.
"If you have a family history of colorectal cancer, or a parent or sibling diagnosed at an early age, you can call your local genetic counselor," Coronel says. "If a mutation is found, it can be referred to us."
The fact that the mutation appears to be widespread could help make genetic screening more efficient, de la Chapelle says. Researchers could start by running a test for the suspect gene, skipping more costly testing for a variety of genes.
Testing for all cancer-causing mutations costs about $2,500, he says, so it would be less expensive to start by looking for just one mutation. "If this is as common as we think, all testing should look at this first," de la Chapelle says.