More Ashkenazi Jews Have Gene Defect that Raises Inherited Breast Cancer Risk

October 01, 1996

More Ashkenazi Jews Have Gene Defect that Raises Inherited Breast Cancer RiskEmbargoed: October 1, 1996
5 p.m. EDT Contact: Christine Westerman
(212) 639-3573More Ashkenazi Jews Have Gene Defect that Raises Inherited Breast Cancer Risk

NEW YORK, Oct. 1, 1996 -- An inherited genetic mutation that increases the risk of breast cancer in Jewish women of Eastern European descent is three times more common than previously estimated, according to a study led by researchers at Memorial Sloan-Kettering Cancer Center.

In the October issue of Nature Genetics, the team reports that the BRCA2 gene mutation is found in one out of every 100 Ashkenazi Jews, a group that includes more than 90 percent of the six million Jews living in the United States. The new estimate is based on an analysis of blood samples from more than 1,200 men and women of Ashkenazi descent.

The study shows the BRCA2 mutation is just as common among Ashkenazis as a similar mutation in the BRCA1 gene that also increases the risk of breast cancer in this ethnic group. Despite the similar frequency of the two mutations, the risk of breast cancer is more than three times higher in Ashkenazi women who inherit the BRCA1 mutation compared to those who inherit the BRCA2 mutation, the research indicates.

"This is a surprise," says Dr. Kenneth Offit, Chief of the Clinical Genetics Service at Memorial Sloan-Kettering, and the study's lead author. "We expected the cancer risk of the two mutations to be about the same."

The findings will likely affect how Ashkenazis are counseled about their risk of inherited breast cancer. "From a public health perspective, we suspect that one in every 50 Ashkenazis carries either the BRCA1 or the BRCA2 mutation, a frequency that is quite high," Dr. Offit says. "We now plan to tailor genetic counseling for individuals based on the origin of their ancestors and the specific mutation they have inherited."

The Memorial Sloan-Kettering researchers set out to determine the prevalence of the BRCA2 mutation among Ashkenazis after publishing a study in the May 1996 issue of Nature Genetics that linked the inherited defect almost exclusively to this population. In the earlier study, they estimated that the mutation occurred in about one in every 333 Ashkenazis. But that estimate was based on the assumption, which the new study disproves, that the breast cancer risk of the BRCA1 mutation, known as 185delAG, and the BRCA2 mutation, known as 6174delT, is the same.

In the current study, conducted in collaboration with New York University and the National Institutes of Health, the researchers analyzed blood samples of 1,255 men and women of Ashkenazi background, without regard to their family history of breast cancer. They found the BRCA2 mutation in almost one percent of the Ashkenazis but not in any of the of the 519 non-Jewish individuals whose blood samples also were screened.

The investigators then wondered whether the BRCA2 mutation shows up as often as the BRCA1 mutation in Ashkenazi women with familial breast cancer. When they analyzed a group of 107 Ashkenazi women with breast cancer -- all of whom had a family history of the disease -- they found a four-fold higher prevalence of the BRCA1 mutation. The increased prevalence of the BRCA1 mutation was observed in both the older and the younger Ashkenazi women with breast cancer.

"It appears that the lifetime risk associated with each of the mutations is different, but we don't yet know why," Dr. Offit says.

Based on the new estimate of the BRCA2 mutation in the Ashkenazi population, the researchers predict that the risk of early-onset breast cancer is increased by 31-fold in Ashkenazi women with the BRCA1 mutation and by nine-fold in those with the BRCA2 mutation, compared to women in the general population. In the study, early-onset breast cancer was defined as that which occurred before 42 years of age.

The BRCA1 and BRCA2 mutations studied by the researchers also have been linked to an increased risk of inherited ovarian cancer, and the BRCA2 mutation appears to play a role in male breast cancer, which occurs rarely.

Earlier studies have indicated that Ashkenazi women who have a mutant BRCA1 or BRCA2 gene face an 80 to 90 percent chance of getting breast cancer in their lifetimes, particularly at a young age. While the risk of inherited breast cancer is higher among Ashkenazi women compared to those in the general population, their overall risk for the disease isn't believed to be increased because most breast cancers are not inherited.

In future studies of Ashkenazis with BRCA1 or BRCA2 mutations, the researchers hope to determine whether medical or surgical interventions can reduce the incidence of breast and ovarian cancer in this population.

Memorial Sloan-Kettering Cancer Center is the world's oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Throughout its long, distinguished history, the Center has played a leadership role in defining the standard of care for patients with cancer. In August, Memorial Sloan-Kettering was named the nation's best cancer center for the fourth consecutive year by U.S. News & World Report.

MSKCC press releases can be found on-line at:

Memorial Sloan Kettering Cancer Center

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