Gene Defect May Provide Cancer Test
A rare genetic defect linked to breast and ovarian cancer is eight times more common among Jewish women of European ancestry, researchers announced Thursday, promising the first inexpensive community screening test for the most common cancer among American women.
Researchers at the National Institutes of Health offered the first direct evidence that an easily detectable alteration in a known breast cancer gene is present not only in high-risk families but also in a specific ethnic group among the general population.
They estimate, for example, that the mutation may account for up to 16% of breast cancers and 39% of ovarian cancers in Jewish women of European, or Ashkenazi, descent under age 50.
Francis Collins, director of the NIH National Center for Genome Research, said the newest finding about how heredity affects breast cancer represents “a sea change in how people think about genetics and public health” because it offers the possibility that large numbers of people can be screened for cancer.
About 3% of the population of North America--about 6 million people--are Jewish. Almost all belong to Ashkenazi families.
*
Against the promise of an affordable diagnostic test, however, scientists say they must weigh the risk that a genetic test designed for a specific ethnic group may be used as a tool of discrimination to deny insurance or employment to people often already singled out by prejudice.
Authorities also question the value of a genetic diagnosis when effective medical treatment options for the disease remain so limited. No new fundamental treatment for breast cancer has been introduced in 20 years, experts said, and survival rates have improved only marginally.
“There was bound to be a stage when we could identify people at risk [for breast cancer] and not be able to do anything about it,” said Mary-Claire King of the University of Washington, who is a noted authority on the genetics of breast cancer.
“We are there now,” she said. “We’re stuck.”
Many women have one or more risk factors for breast cancer. Up to 10% of the women in whom breast cancer is diagnosed--about 183,400 a year in the United States--have a family history of the disease.
When scientists last year discovered a single breast cancer gene, called BRCA1, it raised hopes for a simple test that could be used for all women with a personal or family history of breast cancer. The gene is believed to account for about half of all inherited breast cancers and an equally large number of ovarian cancer cases.
Researchers, however, quickly discovered 60 unique variations of the gene--so many that a useful genetic test was effectively impossible. To ensure that a patient had no hereditary risk, a laboratory would have to test for every single variation. That would be so expensive and time-consuming that it is not practical to screen large numbers of people.
In the new study, published Thursday in the journal Nature Genetics, a team from the Center for Genome Research, the National Cancer Institute and UC San Diego found that a distinctive variation of the cancer gene was so common among Ashkenazi Jews and so rare among the general population that it could easily serve to flag those Jewish women at higher risk of the diseases.
They carried out genetic tests on anonymous blood samples from 858 Ashkenazi Jews in the United States and Israel. They also tested blood from 815 people who were not chosen for their ethnic origin.
The unusual mutation turned up at a rate of 1 in 100 among the Jewish test group, compared with 1 in 800 among the general population.
That rate is at least three times higher than the rate for all the other known variations of the gene combined, and well within the range of many genetic diseases for which limited, routine screening is conducted.
David Goldgar, a University of Utah expert on the causes of breast cancer, called the finding “major” but urged caution.
National Cancer Institute scientist Jeff Struewing, who led the research group, said the scientists are not sure exactly how much this variation of the gene increases a woman’s risk of developing breast or ovarian cancer.
Based on very limited studies of 20 Jewish families with extensive histories of cancer, researchers calculate that if the mutation is present, there is a 90% chance of developing breast cancer and a 50% chance of developing ovarian cancer. But they cautioned that those are preliminary estimates and that more families must be studied.
Researchers on Thursday estimated that a genetic screening test for the mutation could be available in a year, cost less than $40 and be so simple that it could be easily automated. Nonetheless, experts doubt the wisdom of offering it to the public immediately. They are concerned that people will seek the genetic test before medical experts understand the consequences of a positive diagnosis.
“The finding is solid, and there will be a push toward practical testing immediately,” said Arno Motulsky, an authority on genetic screening at the University of Washington. “But without knowing the full information, it will be hard to give practical advice.”
*
Jewish community leaders are helping the National Cancer Institute organize a larger, more comprehensive study involving up to 5,000 Jewish families in the Washington area in the coming weeks. A similar study also is being organized on Long Island, N.Y., where the incidence of breast cancer is among the highest in the country.
“In my view, as much as a mother and a woman as a scientist, I won’t want to be screened until I know what the risk really is for developing breast cancer,” King said. “I would not want my daughter, who is 20, to be screened until we have some non-invasive medical options for a young woman with a positive diagnosis.”
The scenario is symptomatic of an increasingly common, modern medical dilemma.
While a genetic diagnosis offers the possibility of unusual predictive power, DNA is not necessarily destiny. Only rarely can a genetic test reveal that the onset of disease is inevitable. More often, it shows only that a person has inherited a risk of developing a disease.
Earlier this week, scientists announced that they have located three-fourths of all known human genes and determined the function of about 10,000 of them, paving the way for scores of new diagnostic tests for diseases ranging from cancer to Alzheimer’s. Already, laboratories are testing for genes associated with 256 different diseases.
Although it is illegal to refuse someone a job based on a genetic diagnosis, health insurers can and often do cancel insurance coverage by declaring genetic test results to be evidence of a pre-existing condition, experts say.
Medical information from a genetic test also can affect more than a single patient. It can alter a couple’s decision to have children, or reveal sensitive medical information about family members who unknowingly may share the same hereditary risk of a disease.
The newest genetic insight into the nature of breast cancer lends all these concerns a new urgency.
“Our findings are quite simple and the data is quite simple,” said Lawrence C. Brody, a researcher at the National Cancer Institute’s Laboratory of Gene Transfer who helped perform the study. “It is the implications that are complex.”
(BEGIN TEXT OF INFOBOX / INFOGRAPHIC)
Information Hot Line
For more information, call the National Cancer Institute at (800) 4-CANCER.
Institute specialists can answer questions in English and Spanish about the newest breast cancer study and offer other sources of information on counseling, risk factors, and testing options.
