Angelina Jolie's 'Jewish Genetic Mutation': Breast Cancer Gene Is Common in Israel, but Few Opt for Preventive Mastectomy

A study of 5,405 U.S. women with the common Ashkenazi Jewish mutation that increases carriers' risk of breast cancer, who were treated at the Mayo Clinic during the 1990s, found 45 percent chose prophylactic mastectomy, like Angelina Jolie.

Dan Even
Dan Even
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Dan Even
Dan Even

The "faulty" gene that Angelina Jolie credited with her decision to have a preventive double mastectomy is one of three genetic mutations known as "Ashkenazi Jewish mutations," which are common among Jews of Eastern European descent and increase their carriers' risk of developing breast cancer. Nevertheless, relatively few Israeli women choose to undergo the same preventative surgery.

Two mutations on the BRCA1 gene raise the risk of breast cancer by 70 percent, and one on the BRCA2 gene raises the risk by 50 percent. The gene also increases the risk of developing ovarian cancer by dozens of percentage points.

One in every eight Israeli women is at risk of developing breast cancer at some time in her life, from birth to age 90. But a genetic risk factor is found in only about 15 percent of cases.

In recent years, physicians have increasingly debated the need to perform preventative mastectomies to keep women who carry the mutation from developing breast cancer. Most current studies show that those women with the mutation who undergo a prophylactic double mastectomy followed by reconstructive surgery decrease their risk of developing cancer by 75 percent.

The decision to undergo prophylactic double mastectomy has fluctuated over the years. A study of 5,405 American women with the Ashkenazi mutation who were treated at the Mayo Clinic during the 1990s found that 45 percent had chosen prophylactic mastectomy. In 2003, the rate dropped to 30 percent, while in 2006 it rose again, to 43 percent. In the U.S., prophylactic mastectomy and oophorectomy (removal of the ovaries) were promoted under the slogan “No organ, no disease.” In the U.S., the operations are also a source of income for private surgery clinics. But in Israel, where the prophylactic operations are included in general health coverage for women who carry the mutation, some physicians are critical of the method.

A study published in 2008 of 2,677 carriers of the Ashkenazi mutation in nine countries, including Israel, showed that in three and a half years of tracking since they were diagnosed with the mutation, 57.2 percent underwent prophylactic oophorectomy. Of 1,381 women who did not develop breast cancer, 18 percent underwent a prophylactic double mastectomy, according to the study published in the International Journal of Cancer.

The statistics show high rates of prophylactic mastectomy among carriers in the U.S. (36.3 percent), the Netherlands (32.7 percent) and France (25 percent) as compared with Norway (4.5 percent), Israel (4.2 percent) and Poland (2.7 percent).

Cancer treatments in development over the past few years, known as PARP inhibitors, may make the argument moot in the future. The treatments are being studied for their ability to cause the body to repair the Ashkenazi mutation using a sound copy of the gene in the carrier’s body.

The three Ashkenazi mutations are identified in blood tests among 2.5 percent of Jewish women of Ashkenazi descent and 0.3 percent of the general population of women in Israel. When one parent carries the mutation, there is a 50 percent chance that the child will carry it, and when both parents carry the mutation, the risk that the child will carry it goes up to 66 percent, along with an increased risk of repeated miscarriage. Several hospitals, including some in Israel, perform pre-implantation genetic diagnosis (PGD) in in-vitro fertilization to keep the gene from being passed on.

In October 2012, a study carried out by Professor Efrat Levi-Lahad, head of the Department of Medical Genetics at Shaare Zedek Hospital, examined 8,000 healthy Ashkenazi men, and found that 175 of them carried the Ashkenazi mutation. Female relatives of the carriers were also examined, and it turned out that among them, the risk of developing breast or ovarian cancer was between 75 and 80 percent. The researchers recommended a policy of general genetic testing for the presence of the Ashkenazi mutation among the entire Ashkenazi population in Israel. However, only 30 percent of women – who as first-degree relatives of women with breast and ovarian cancer, are eligible for testing – are actually tested.

A 2011 archive photo of actors Brad Pitt and Angelina Jolie.Credit: AFP

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