The author and her two children in. She asked for genetic testing, as many do, in part to protect their own health as they grow
PHOTO :. © April SAUL
Rarely could I be described in a title in The New York Times , which is why I stayed on a earlier this fall. "Study of Jewish Women Shows a link to cancer without family history," said history September 5 Uncomfortable, I read on. "Women of Ashkenazi Jewish descent who tested positive for genetic mutations that cause cancer in random screenings have high rates of cancer ovarian and breast cancer, even when they have no family history of the disease, researchers reported on Thursday. "
Hmmm.
science has been my professional home for the past 13 years and in that time, I have written and spoken about genetic testing with dozens of experts from the edge of field cut. I chronicle the scientific advances, ethical dilemmas, life saving tests, the anguish he ignites. I've never turned the lens on my own DNA.
Suddenly there was no escaping it. My parents are both of Ashkenazi origin. To my knowledge, nobody on either side of my family has ever had breast or ovarian cancer. But suddenly I saw how a mutation in the genes described in this article BRCA1 and BRCA2 , had slipped unnoticed through a small family of my father, heavy on chromosome Y therethrough; his older brother; my three cousins, two of whom are men. I remembered that my paternal grandfather had suffered from prostate cancer, which eventually spread to her bones and killed him. My uncle had the disease, too. In addition to their storied role in breast and ovarian cancer, BRCA mutations are associated with prostate cancer in men. I had long known that Ashkenazi Jews are more likely to carry mutations in these genes. But that was as far as my knowledge went.
When I probed the numbers, they were not particularly reassuring. A quick Google search, why had I never done this before? -revealed That one in 40 Ashkenazi wear BRCA mutations, compared with as little as 800 in the general population. Like almost all cancer-related genes, BRCA1 and BRCA2 were discovered in families riddled with disease. But the September study, led by Ephrat Levy-Lahad, a medical geneticist at Shaare Zedek Medical Center in Jerusalem, argued that other families shared a high risk if they had the same mutations.
The newspaper article that has everything triggered, published in early September.
PHOTO: © April SAUL
Several authors, including Mary-Claire King of the University of Washington, Seattle, BRCA1 's discoverer, say all women, regardless of family history should know if they have dangerous mutations in BRCA1 and BRCA2 . Other experts are not yet convinced. Perhaps even more controversial is that to track tens of risk genes discovered in the last decade, some tenuous linked to cancer. I could have written a nuanced story Science on both sides of the debate. But when it came to my own health, 486 Israeli women with BRCA mutations, half without a family history, but all very vulnerable to cancer, was all it took.
Time seemed gasoline. I am 38 years old; ovary removal in BRCA carriers recommended by 40. I called the hospital in suburban Philadelphia where my children, now 2 and 5 years, were born and spoke with a genetic counselor. She has a family history and agreed that yes, testing BRCA was worth it, and yes, the insurance would probably cover it in my case.
I booked an appointment. I was about to discover my own tape of the new world of genetic testing for cancer, which would take me beyond BRCA and a more uncertain ground.
THE AUTOMATIC DOORS SWISH soundlessly open as I step into the hospital's cancer center. A genetic counselor with brown, curly hair and glasses approach me, smiling, clipboard in hand. In her office, she released a pedigree of my family sketched in pencil square for men, for women circles, slashes through those who died in the cause of death scribbled next to them. I thought I just loan-after all, I am here only to BRCA tests, and only because of my ancestry, but it turns out I did not. Hysterectomy my grandmother included the removal of her ovaries? (I hazard a guess and members of the family request after the fact, we do not know if I got it right.) Is my grandmother die of stomach or colon cancer? "She was in her 0s," I said. I still carry a vague memory of his visit to the hospital, in 3 years, shortly before his death. "Does it matter when someone's that old ? "
The advisor pulls a sheet of paper and places it on the table. There is a list of 21 genes associated with breast and ovarian cancer. Eleven are in pink and gray labeled "high risk"; three are in the purple category "moderate risk"; and seven are turquoise and described obliquely as "new genes." This is Breast / Ovarian Cancer Panel of GeneDx company in Gaithersburg, Maryland, but as is often the case in oncology, many genes contribute to of other cancers, too. it confers a risk of stomach cancer 40% to 83%. removing the stomach is recommended if the test is positive. another, TP53 , confers a risk cancer in women and a chance of 73% for men of almost 100% TP53 cancers include brain cancers and sarcomas
regarding two genes. on the panel BRCA1 and BRCA2 , there is little doubt that in families predisposed to cancer, screening saves lives: in-depth study of BRCA carriers found that those who have their ovaries removed were 80% less likely to die from ovarian cancer and 50% less likely to die of breast cancer. Prophylactic mastectomy appears to reduce the risk of breast cancer by at least 95%.
But many other genes for which the test was discouraged some years because their impact on health was uncertain are "now regularly offered," said Kenneth Offit, chief of clinical genetics at Memorial Sloan Kettering cancer Center in New York City. "This is the paradox that we fell in." Just as risk genes more cancer were discovered, the cost of their deep sequencing. the result is a proliferation of panels designed to decipher DNA.
how each of these genes increases the risk in individuals, and at what age, is often blurred. "clinical work came out ahead of us," says Fergus Couch, an authority on BRCA and other breast cancer genes at the Mayo Clinic in Rochester, Minnesota. "The [sequencing] The technology changed so fast" that "we did not have time" to develop answers to questions from patients and physicians now asking.
In the summer of 2013, GeneDx launched its breast / ovarian cancer-Panel stimulated in part by the decision of the Supreme Court against the patent claims of Myriad Genetics on BRCA genes. Other companies, including himself and Ambry Myriad Genetics and academic medical centers, jumped with panels of several dozen genes linked to a range of cancers. "We are really looking at things that will provide the physician the possibility of a treatment plan," for example, adding increased surveillance, said Sherri Bale, Director General of GeneDx. The genes on company boards are " a moving target, "she said, with the added culprits and sometimes deleted based on the available scientific evidence. Bale believes that the panels, which cost in the neighborhood of two or three thousand dollars, are suitable for high-risk families, but not for the general population.
THE LIST OF GENES 21 sitting between us, and I consider everything I could learn by simply saying yes. The counselor does not advocate that I sign for the full panel. But it draws my attention to a gene in the purple group to moderate risk CHEK2 . The list of cancers beside him is long: "Breast Female, Male Breast, Colon, prostate, thyroid, kidney, endometrium (serous), ovary." I am vaguely familiar with CHEK2 as a breast cancer gene from my own statement. "Is CHEK2 more common in Ashkenazi?" I ask, still stuck on the heritage that my cancer driver and why I'm in this room to begin.
"No," the adviser responds. But in addition to the prostate, my paternal grandfather had colon cancer. "He was in his 70s!" I protest. Nevertheless, CHEK2 test for me worth considering, the counselor says. A CHEK2 mutation could approximately double the risk of cancer breast, at least 20%. MRI and annual breast mammograms would probably recommended.
I saw thwart. Adding another gene for the test had never occurred to me. and yet, if the test is positive, the share price seems relatively benign and potentially save lives.
"Let's do it," I say. We talked for about 40 minutes.
the counselor fate . a consent form "There is one more thing," she explains a text block is titled It reads, in part. "variant of uncertain significance (SUV)." "I can learn a SUV was identified by this test. this means that a genetic change (variation) has been identified, but it is unclear whether the variant can cause cancer. "A particular cancer gene may have thousands of variations, some showing in a handful of families around the world. Some variants are a major contributor to the disease, while others are benign changes in DNA that, in practice, mean nothing.
again, my years of medical journalism were able to prepare. "How common are these in BRCA and CHEK2 ? "I ask. for BRCA1 and BRCA2 , the counselor explains, about 2% of people have an SUV. (I learn later that VUs rates fluctuate according to the company offering the test.) She does not know about CHEK2 , but is happy to discover. it also stresses that looking for an SUV does not affect medical advice and that the hospital contact me if an SUV is then reclassified as either harmless or pathogens.
I push aside my hesitation, sign the forms, and am off to the lab for a blood test.
Driving home, my intolerance of uncertainty rears its head. Do I really want to know if I am an SUV? What's the point? This afternoon, I send the advisor by email. I told him I'm worried that learning VUSs "cause me anxiety and there will be no benefit in having this information. I wonder if it is possible not to receive information on any SUV which can be found in the tests. ... is that an option? "
How a BRCA1 mutation raises the risk of breast cancer of a woman depends on her age, family history and other variables, such as the examples below illustrate.
She wrote back quickly and pleasantly. She checked with GeneDx and learned that, for regulatory reasons, they are obliged to share information if an SUV is found. It will ask its medical director if the hospital can keep an SUV find me. But she also wondered if "you feel anxious not know whether or not you can be contacted in the future about a reclassified SUV. ... There are chances that you not have an SUV and you may feel a relief to know that you do not have it. "
She later wrote to say that his medical director is retained a comfortable SUV if no pathogenic variants turn up And there's more good news. She learned that the rate of SUV for CHEK2 , by GeneDx, is only 1.6%, much lower than it thought that the well-origin estimates vary depending on who you ask. I SHELVE my inner dialogue where the information I want.
Two days later while GeneDx is the analysis of my DNA, I'm on the phone with Susan Domchek, an oncologist the study of the breast cancer genes at the University of Pennsylvania. We discuss cancer risk genes in people with no family history of disease. Spontaneously, Domchek raises CHEK2 testing . "We do not know how to integrate it into patient care, "she complained, referring to HIV-positive women and their families. "What percentage of the time it really add anything to the situation?" I do not speak my own CHEK2 test is in progress. Instead, I learn about the frequency of CHEK2 mutations in the general population. Domchek the response that people only about one in 0 in the United States is a carrier helps me breathe.
Domchek is one of many researchers trying to clarify the interaction between genes and cancer diseases. With Offit, Couch, and others, has developed an online registry called PROMPT which opened earlier this fall. It aims to save thousands of people who have had the test panel offered by a host of companies, including GeneDx, Ambry, Myriad, Quest Diagnostics, and Pathway Genomics. Their goal is a database that will help them examine how specific gene variations affect health.
"We need to experience the world with all these panels," said Couch. It also highlights an irony: Despite some concern, scientists need him as panel testing to continue, because it is their best shot to collect sufficient data to address research questions. At the same time, "You do not want to do science ... at the expense of the patient," he said. Couch is part of an international consortium called ENIGMA working to sequence the breast cancer genes from 40,000 cancer patients and healthy people. the project nailing the risk conferred by different mutations and study the impact of VUSs about the disease.
multigene panels for the risk of cancer are increasing and change, including that of 21 genes associated with breast, ovarian and other cancers, shared with the author before his own test
DATA :. GENEDX ONCOLOGY PROGRAM
outside the United States, signs of cancer genes are largely limited to research settings, and investigators often do not share information about the changes that have a small or unknown risk. There is much debate about what to say volunteers. "We struggle with it," said Hans Ehrencrona, a clinical geneticist at the Lund University Hospital in Sweden. "Where do you draw the line, no one knows for sure."
Every woman in Sweden who receives BRCA test is now offered the chance to enroll in a study in which it tested for 63 other cancer genes. The results of only seven of them are shared with participants. Many moderate risk genes are not on the list, said Ehrencrona, who is helping lead the effort. As an example, he points out, " CHEK2 is quite common in Sweden. We will not return. "
ONE TUESDAY MORNING IN OCTOBER minutes after a work conference after the call, my phone rings." I have your results, "the adviser announces. For 19 days I met her. "What do you want to know?"
Well, pathogenic mutations, of course, I say
There is good news, she said :. No pathogenic mutations were detected in one of the three genes.
relief rushed through me. "Do you know about any SUV?" Application does. I think CHEK2 , and the SUV of 1.6%, it cited. What are the odds? "Of course, "I said.
" There was no meaning unknown variants detected in BRCA but unknown significance variant was detected in CHEK2 , "she told me. reading the report GeneDx, she explained that my SUV is a deletion of 15 nucleotides of DNA. the variant was found in two men with prostate cancer, and in vitro analysis suggests that causes partial loss of function of the gene.
I expect distress, ringing in my ears, fear coiling in the pit of my stomach. instead, I almost laughed. I think, "that's it? that's what's shared with patients today?" Two men with prostate cancer cells in a petri dish, a loss of function that may or may not result pathogenicity. This does not deserve my mental energy
"People need to become more comfortable with uncertainty," Sharon Plon, a clinical geneticist at Baylor College of Medicine in Houston, Texas, told me a few days later. But she stressed that the recognition of uncertainty "does not mean that we do not know anything." For many families suffering from cancer, large panels provide constructive advice.
I am writing to my cousin in San Francisco to share my test results; she is the only woman close relative of my father's side, where the cluster of cases of cancer and she is more familiar than most signs: His mother. nonbiological my aunt, is the fight against ovarian cancer and signed for a panel of 41 genes offered by the University of Washington, Seattle. She tested negative for all.
My cousin asked me examine the same panel, which has now expanded to 48 genes. in the end, I explained in my message to her, it was not something I wanted. "I know the signs are often discouraged , "she wrote back. There is a view that it does not share. Even without a clear-cut action plan, she wants to know some message from his DNA carries its future. The only reason she avoided testing for itself is because insurance is unlikely to pay for it. "Knowledge is power," she wrote. "I do not mind at all."
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