Ashkenazi Jews weather news of another gene flaw 250 callers seek facts on colon cancer link

THE BALTIMORE SUN

Across 1,000 years of traceable history, Ashkenazi Jews have ridden countless waves of success and hardship. This may partly explain the sober reflection that followed last week's news that yet another cancer-causing gene runs through Jewish families with roots in Eastern Europe.

Researchers at Johns Hopkins Oncology Center announced that they had identified a genetic defect shared by about 700,000 Jews that predisposes them to colorectal cancer. The news had a familiar ring: Just a few years ago, scientists found that Ashkenazi women are at risk for two mutations that trigger breast cancer.

Surely, the latest news was received in some quarters with the age-old question, "Why the Jews?"

But some had a different perspective.

"I'm a Jew of Eastern European descent, so I can speak only for myself -- it's a constant concern, but so are taxes," said George Berlin, a history professor at the Baltimore Hebrew University. "We're not different than any other group where a predisposition has been found to a particular illness."

Within three days of the Aug. 25 announcement, 250 people called a Hopkins hot line (410-955-4041) to ask about a blood test that is being offered to Ashkenazi Jews who have a family history of colon cancer. Hopkins opened a second phone line to handle the deluge.

Callers came largely from Baltimore's large Jewish community but also from cities across the

country.

"No one has been hysterical," said Marijayne Bushey, a research assistant who has handled many of the requests. "Everyone who calls is at the very least interested, at most concerned. Everyone's just happy to have whatever information we can provide at this time."

Test recommendation

Scientists who made the discovery are recommending the test for adult Jews of Eastern European descent who know of at least one relative who had colon cancer. People who test positive for the gene can use the information to get examined early -- and often -- for signs of suspicious growths in their colon.

Surgery can cure many patients, but only if the disease is caught early.

When she heard the news, Laurie Kramer of Baltimore remembered an uncle once treated for a precancerous polyp.

"As an Ashkenazi Jew, when I found out there is this test for a disease which can be prevented -- that, to me, said I should probably get tested," said Kramer, 37. "There are some genetic diseases like Huntington's disease where, if you find out you have it, there is absolutely nothing you can do about it."

Kramer works at a Hopkins medical unit, writing software for a computer database that serves as a worldwide clearinghouse for information about the human genome, the set of genes that is unique to humans. Although she is comfortable with genetic principles, she is worried that insurance companies might use genetic information to discriminate against people.

"I think it's a very big issue that the country has to grapple with," she said.

The Ashkenazim can be traced to the 10th century -- to the towns and cities of Germany where Jews were forced to live in designated sections.

They seldom socialized with non-Jews and hardly ever married outside their community.

"Typically, the only contact they would have with the non-Jewish community would be in business matters," Berlin said.

Beginning in the 13th century, "a variety of expulsions over the course of centuries" caused groups to migrate to Poland and, later, Russia. They formed the nucleus of the vibrant culture that now is associated with Eastern European Jewry but had its roots -- genetic and otherwise -- in Germany.

Dr. Bert Vogelstein, the world-famous cancer researcher who helped identify the gene, said it is not surprising that science has turned up a few harmful genes that run through Jewish families. Vogelstein said such genes can cluster in any ethnic group that is relatively small and has spent many years in geographic isolation.

Passed along

The phenomenon is known as the "founder's effect." Somehow, a mutation occurs in a particular person and gets passed to future generations. The gene remains confined to the ethnic group because its members marry among themselves.

When the mutation "starts with a small number of individuals, then it becomes genetically isolated over time," Vogelstein said. "Just by chance, some mutations will increase in frequency, some will decrease."

In the case of Jews, persecution also may have played a role.

Over the centuries, periods of high growth in Europe's Jewish population were often followed by massacres. "You have this tremendous population decimation, then the next wave of population growth is going to start with a relative handful of people," said Gloria Peterson, a cancer epidemiologist who worked on the Hopkins study.

This caused "population bottlenecks" through which deleterious genes could pass by chance, remaining confined to a relative few.

Vogelstein, a Jew whose ancestors came from the Ukraine, said the same principle causes beneficial genes to cluster within ethnic groups -- an important point seldom stressed.

"No one will ever find them because there is no good way to look," he said.

The founder's effect is starkly demonstrated among the Amish, an extremely close-knit group that suffers from a host of unusual metabolic diseases.

Other cancers have been found to run within ethnic groups besides Jews.

Melanoma, a deadly form of skin cancer, is common to people of Scandinavian descent, probably because they are not amply supplied with the skin pigmentation that filters harmful rays of the sun.

"In the Chinese population, there's an increased risk of liver cancer," said Peterson, although that is presumed to result from dietary and environmental causes.

African-Americans suffer disproportionately from prostate cancer, and researchers are investigating the possibility that an inherited mutation is to blame.

An inherited mutation for a rarer type of colon cancer called Lynch's syndrome has been found among certain Navajo families.

The disease is named for Dr. Henry Lynch, a cancer researcher at Creighton University in Omaha, Neb., who first described the cancer in the 1960s. Later, Vogelstein's lab identified the culprit gene and devised a way to test for it.

More recently, Lynch found the gene among members of a Navajo family that was "riddled with cancer."

He decided to look for the same mutation elsewhere on the sprawling Navajo reservation that straddles Arizona, New Mexico, Utah and Colorado.

Lynch chose four families with histories of colon cancer.

"Lo and behold, we found the identical mutation in all four of those nuclear families that were dispersed remotely from the original family," Lynch said. "That's the founder effect."

Among Jews, the colon cancer mutation was detected in 6 percent of healthy Ashkenazim whom the Hopkins group studied. Meanwhile, it was detected in 12 percent of Ashkenazim who had the disease and in 28 percent of those who had colon cancer and at least one relative with the disease.

Double the risk

Carrying the mutation doubles one's risk of getting the disease, which is already one of the most common cancers in the U.S. population.

Between 9 percent and 15 percent of Ashkenazi Jews will get colon cancer; as many as 30 percent who carry the gene will get the disease.

Vogelstein said he wouldn't be surprised if other mutations that trigger colon cancer were concentrated within other ethnic groups. Such mutations would be similar in nature -- subtle misspellings along a stretch of DNA that is 9,000 characters long -- only this time, it would occur in a different place.

The mutation was found among Jews, in part, because they were easy to study.

Hopkins had a built-in database of more than 700 Jews who had donated blood to be tested for the gene that causes Tay-Sachs disease, a neurologic condition that runs among the Ashkenazim. About 300 Jews had donated tissues for other tests unrelated to cancer.

These donors served as "controls," enabling a genetic comparison to Jewish patients who had been treated for colon cancer. All this was facilitated by the fact that Hopkins -- along with collaborating hospitals in New York and Los Angeles -- draws patients from communities with large Jewish populations.

Pub Date: 9/01/97

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