Using Genetics, Family History, and Environmental Factors to Make Health Decisions
Health care gets personal with precision medicine. It targets patient facets to recommend a specific approach to health.
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When Michelle McIntyre’s aunt called a few months ago to talk about the fact that McIntyre might have inherited a faulty gene, one associated with a high risk of cancer, she didn’t know what to do with the information. “I thought but I’m only 39, and I’m healthy. Why are we talking about this?”
McIntyre’s uncle (brother to her father and her aunt) had just passed away. He died of stomach cancer that had reached stage 4 (out of 4) before it was diagnosed and had spread to his lungs. Now her aunt was telling her about meeting two distant cousins, a mother and daughter, at a large family reunion the previous summer. Both women had had their stomachs removed because they had the CDH1 gene mutation. One cousin’s stomach already displayed stage 2 cancer when it was removed, and the other cousin had faced breast cancer as well. McIntyre’s aunt was concerned that the CDH1 gene mutation ran in the family, and she raised the idea that McIntyre undergo genetic testing. “I was confused. I had never heard of the CDH1 gene, but I googled it straight away,” McIntyre said.
Her search revealed that men and women with the CDH1 gene mutation have a high risk for a gastric cancer that involves the stomach lining, which is difficult to detect in the early stages of the disease. For this reason, removing the stomach before the cancer can form may be recommended. Women with the CDH1 mutation are also at increased risk for lobular breast cancer. And there is an increased risk for colon cancer as well.
McIntyre also emailed her primary care physician, who referred her to Kaiser Permanente’s Oakland Medical Center for genetic testing and counseling. Two days later, she sat with a counselor who took a detailed family history of cancer along with two vials of blood. “She walked me through the potential outcomes and options and gave me a lot of information,” said McIntyre. Three weeks later, the blood test results were in, and McIntyre learned that she had tested positive for the CDH1 mutation.
“That was a long three weeks and a difficult result to process, but the counselor had prepared me. It’s not just about choosing an option. There’s the emotional and psychological impact of all this to manage, too,” she said. McIntyre opted to have her stomach removed as a preventative step and to get screened routinely for breast and colon cancer.
What McIntyre experienced is called precision medicine — the next paradigm shift in health care, according to Leslie Manace, a physician with Kaiser’s Department of Genetics. “We are going to the molecular level, sequencing the individual’s DNA, looking for genetic variations, and combining that information with the patient’s family history and environmental factors [like diet, exercise, and smoking],” said Manace. In the past, medical decisions were primarily based on the results of large studies that were applied across all patients, more of a one-size-fits-all approach, she explained. “Precision medicine is a logical extension, using the same logic but personalizing it,” said Manace.
Kaiser’s genetics department, based out of Oakland and Richmond, has five physician geneticists and 18 counselors who saw over 8,000 cases last year. Cancer genetic counseling (like McIntyre’s case) is a large part of what the department handles.
“A simple blood test may yield profound information,” said Manace. Maintaining patient privacy and autonomy are essential to precision medicine and genetic counseling, she added. Patients can opt out of the genetic testing that is offered, but she finds that a substantial majority of patients pursue the testing and want the information. “It’s a nondirective field. We meet people where they are considering their age, health profile, a number of variables, and let them make their own decisions.”
Gregory Tranah, Ph.D., has been the director of the Center for Precision Medicine at Sutter Health in Oakland for the past two years. “In many cases, it’s difficult to know how to best treat a patient,” said Tranah, “Precision medicine is the research that leads to a better understanding of how a disease progresses and can be treated.”
Sutter Health is using precision medicine to study multiple sclerosis, a debilitating neurological disorder that affects nearly a million people in the United States. Multiple sclerosis is complex, with three different subtypes, a range of presentations, no blood test to diagnose it, and several treatments available with different effectiveness and side effects. “In neurology, it gets tricky because unlike cancer, we can’t sequence every part of the brain and every neuron in the body,” said Tranah.
However, new tools to analyze large, complex sets of patient data, another application of precision medicine, are now available, explained Tranah. Sutter is collecting information directly from its MS patients in Northern California and through its electronic health records to better identify and understand the patterns of MS. “We are drilling down deep into the details of the disease, which has often impacted these patients for years,” he said.
Oakland resident Audrey Fisher, now 64, was diagnosed with MS at age 50. Initially she lost functional use of her hands, had difficulty walking, and could no longer work full time. “The diagnosis was scary, because I didn’t know how my MS would progress,” said Fisher. She has taken four different MS drugs over the years with varying success. When her neurologist mentioned participating in the study, Fisher was on board. “I believe that anything I can do to help us gain a better, more precise understanding of MS for those of living with it everyday is important,” she said.
“Only by understanding the cause of MS can we figure out the best way to treat it,” said Tranah.
Other areas that Sutter Health is exploring with precision medicine include Parkinson’s disease, dementia, migraine, metastatic cancer, and cardiovascular disease. “Our patients are partnering with us and contributing to these new discoveries,” added Tranah.
“Angelina Jolie’s announcement that she had inherited the BRAC1 gene mutation from her mother and her openness about the decision to prophylactically have her breasts removed was a turning point [for precision medicine],” said Manace. Kaiser has seen a four-fold increase in cancer genetic screening since Jolie’s story was reported. “We don’t just go and test everybody,” she said. “But with something like BRAC1 and breast cancer, there’s a very clear risk-benefit rational to screening.” she explained.
“Precision medicine is not just for the rare disorder, which will effect 5 percent to 10 percent of the population or less,” said Manace. There have been rapid advances in the genetic testing technology, and the interpretation of these data is catching up, she explained. Pharmacogenetics — understanding the effect of genetic factors on how we individually respond to drugs — is an example of precision medicine extending to the whole population, Manace pointed out. “Precision medicine is like detective work, we’re putting together the pieces of a huge puzzle.”