High Frequency of Ovarian Cancer Markers Found in Ashkenazi Jewish Women

The finding of a high frequency of genetic markers for both breast and ovarian cancers among Ashkenazi Jewish women has prompted a call for genetic testing for all breast and ovarian cancer victims in this population, regardless of family history.

A new research study by an Israeli medical team found the genetic markers, BRCA1 and BRCA2 mutations, among women with sporadic breast and ovarian cancers as well as familial cancers. Accordingly, the study recommends that all Ashkenazi Jewish women with these gynecologic cancers undergo genetic testing to determine whether the genetic markers are present. Finding the BRCA1 and BRCA2 mutations would differentiate between carriers and noncarriers, thereby providing immediate significance to a carrier’s family members.

The study, coauthored by Uziel Belier, MD, David Halle, PhD, Raphael Catane, MD, Bella Kaufman, MD, Gila Hornreich, MD, and Ephrat Levy-Lahad,MD, all from Shaare Zedek Medical Center, Jerusalem, Israel, was published in the November issue of Gynecologic Oncology.

Study Adds to Debate Over Value of Genetic Screening

“This study contributes to the ongoing dialogue in the medical community regarding the long-term value of genetic testing,” stated Peter Schwartz,MD, Professor of Gynecologic Oncology at Yale University and President of the Society of Gynecologic Oncologists. Dr. Schwartz added, “Dr. Beller’s recommendations could conceivably be implemented in Israel where its national health system covers genetic testing. In the United States, such testing is not generally covered by medical insurance programs, making implementation of this new widespread screening technique impractical at this time.”

Ovarian cancer, the most lethal of all gynecologic malignancies, has no detectable premalignant stage and is therefore usually diagnosed only in advanced stages. While screening the general public has not been found to be effective, high-risk groups may benefit from such an intervention. A recent series of research studies have examined protocols for identifying BRCA1 and BRCA2 gene mutations in high-risk populations, indicating an inherited susceptibility to breast and ovarian cancers. Analysis of these genes has revealed more than 100 pathogenic mutations in each. The mutations are generally “private.”

One high-risk population group, Ashkenazi Jews, have been found to have three recurrent mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. The presence of these recurrent mutations may explain 30% of breast cancer in Ashkenazi Jewish women under age 40 and 100% of cases of both breast and ovarian cancer in these women.

Since family history is difficult to track among Ashkenazi Jews, the Shaare Zedek Medical Center examined series of Ashkenazi women with ovarian cancer to determine how the gene mutations contributed to their disease. A total of 29 Ashkenazi women were included in the study, 6 of whom had breast and ovarian cancer and 23 of whom had ovarian cancer only. The patients were recruited for the study from September 1995 through May 1996. All the patients were alive at the time of the study, regardless of the time of diagnosis.

Study Results

All six women with both breast and ovarian cancers had one of three recurrent mutations in equal frequencies. Three of the six women had no family history of the disease. The study also revealed that a breast cancer diagnosis always preceded the appearance of ovarian cancer.

Of the 23 women with ovarian cancer only, 11 were found to carry the mutated genes. Of that group, four had a family history of ovarian cancer, four had at least one relative with the disease, and three had no family history of ovarian cancer whatsoever.

Dr. Belier and his team concluded that, given the high proportion of ovarian cancer in Ashkenazi Jews, a screening intervention is recommended to provide additional information to the overall population of this group, regardless of family history.