Being the first mutation to enter Jewish consciousness, 185delAG became the best-studied, most worried-over piece of DNA in the world. Largely because of it, more people have been tested for BRCA1 than for any other human gene. An initial screening of the broader Jewish population, conducted by the NIH in 1996, followed the procedure that had succeeded with Tay-Sachs testing. Some 5,000 volunteers in the Washington, D.C., area were recruited with the aid of rabbis and community health officials. They provided researchers with DNA samples and histories of any cancers in their families. As before, the people who stepped forward offered to help even though, in this first snapshot of the problem, they were not given their individual test results.
From the NIH study and others, scientists
that not every BRCA carrier was going to be affected, because the mutations were not fully penetrant. Penetrance is a technical term signifying that a powerful gene may pull its punches. Because of incomplete penetrance—because of healthy elderly carriers like Shonnie Medina’s grandmother, Dorothy—the risk of cancer from 185delAG and other BRCA mutations must be expressed in terms of probability. The range of estimates is wide. The most hopeful studies suggest that just half the carriers will get breast cancer during their lifetimes, the least hopeful that 90 percent will. The number given most often is 80 percent. The penetrance of ovarian cancer is lower, in the neighborhood of 40 percent. Something blunts the thrust of the gene, but no female who is a carrier can count on that happening.
When news of the Ashkenazi BRCA was conveyed to the Jewish community, it was often oversimplified in the direction of alarm. Women tended to overestimate their risks of carrying a mutation if there were any reports or hints of breast cancer among their relatives. Newspapers and magazines published articles by or about Ashkenazi women agonizing over BRCA. According to surveys, Jewish women were much more likely to visit a genetic counselor than other minorities were. The women knew that if they took the test and it was positive, the next dilemma would be whether to have a preventive mastectomy or to try to circumvent the risk with extra mammograms and closer surveillance. The knowledge was like the apple that Eve offered Adam. A single bite of the apple tempted another, as sisters, aunts, fathers, and daughters submitted their DNA for analysis. Positive results brought fear and shame, and negative results, relief and guilt, the riptides of emotion dividing families.
Pressing to save lives, some scientists recommended large-scale screening of the Ashkenazi population. Others said no, it is too soon, better wait for additional studies to be completed. But how would such studies be used? Would health insurance companies call BRCA a preexisting condition and deny coverage? There were laws against genetic discrimination in health policies, but they didn’t apply to life insurance policies. Would Jews become an uninsurable class of people?
Orthodox Jews wrestled with all of these anxieties and more. Within their circle, as Rabbi Ekstein knew better than anyone, a diagnosis of breast cancer could prompt
a woman to seek treatment in another city, lest the people at home find out. High in her mind were her children’s marital prospects. If a young person was told that a BRCA mutation had been detected in her family or, G_d forbid, that she carried a mutation herself, at what point in her courtship was she obliged to disclose the information to her potential spouse? Should she then be rejected? Ekstein, unable to devise a work-around for couples in his care, found the situation deplorable. “What is the advantage of screening for a condition, a mutation, that has no treatment?” he demanded to know. “It is just making more tragedy. For the rest of her life and her future generations, she will be burdened with worry.” Ekstein came out strongly against the BRCA test.
But like it or not, the Jewish BRCA carriers were the vanguard. Thanks to the 185delAG mutation and its two companions, BRCA has become a metonym of cancer risk for every woman. When Jewish women enrolled in research to test the gene’s penetrance, the results were applied to all other ethnicities, where mutations were not as common. A genetic aberration conceived in isolation from the rest of the world was donated to the world through science, adding to knowledge of BRCA’s universal behavior. If there was one disadvantage to using Ashkenazim in genetic studies, it was that their blood relatives were harder to come by than in other groups. Their extended families tended to be smaller, their pedigrees pinched off because of Jewish losses in the pogroms of Eastern Europe and, more recently, the Holocaust.
In New York, Chicago, Los Angeles, and other cities, demand for the tests surged, in part because Myriad Genetics, the company that owned the patent for BRCA testing, promoted the service directly to doctors and consumers. The company reported in 2008 that the number of people taking the test was growing by 50 percent every year. The negative findings well outstripped the positives, but that didn’t dent the demand to know. Myriad estimated that half a million BRCA carriers in the United States remained to be detected, including 150,000 who were Jewish. Among 5 million American Ashkenazim, you could figure on 50,000 carriers of 185delAG. Nobody in the genetics profession was calling 185delAG an Ashkenazi mutation any longer. By this time it had turned up in a dozen distant places along the spidery trail of Jewish migration, including New Mexico and the San Luis Valley.
Iona’s aunts Wanda and Lupita, who had tested positive for the mutation in 2007, were diagnosed with breast cancer in 2009. Wanda’s case was advanced, and she died that spring. The spate of bad news made it impossible for Iona to put off her BRCA test any longer. She was having trouble sleeping. “I realized I was being selfish,” Iona said. “It would be selfish of me to put people through what Wanda and Shonnie did, if I could do something about it.”
Leaving a blood sample at the lab, Iona went home to await the result. Her heart started beating rapidly. To work off steam, she did kickboxing exercises against a heavy punching bag. One day she felt a stabbing pain in her chest and was taken to the emergency room, believing she’d had a heart attack. Instead, she had pulled a muscle. Then the genetic counselor phoned: Iona, like her late sister and at least 10 of her close relatives, was positive for 185delAG.
In 2010 Iona enrolled in a new program at Penrose Cancer Center in Colorado Springs. Called the High Risk Breast Clinic, it offered BRCA carriers a free consultation with a breast surgeon, along with mammography or an MRI scan. Signing up for the program made Iona feel better. Her first MRI was negative. In her mind, she had taken her breast- and ovarian-cancer risk under control not through surgery but through watchful waiting, the strategy Rabbi Ekstein favored. Preventive mastectomy was off the table, and after learning more about ovarian removal (another preventive measure) Iona decided she didn’t want that operation either. The fact that she had taken birth-control pills for years was somewhat protective against ovarian cancer.
The anxiety attacks, the sense of being overwhelmed, were past, but in relating this, Iona spoke rapidly, giving wide berth to her emotions. “Experience shows,” Ekstein says, “that even the most highly educated of individuals have difficulty using intellect to dominate emotions.”
Iona knew the answer deep in her DNA, knew the 2,500-year-old mutation that had found its way into her body, yes, she knew. She knew what her headstrong sister hadn’t. Though Shonnie would not have cared.
Jeff Wheelwright is a longtime contributor to DISCOVER. His new book, The Wandering Gene and the Indian Princess: Race, Religion, and DNA, was published this month. Excerpted with permission of the publisher, W.W. Norton & Company, Inc.