Genetics can help to predict bad reactions to chemotherapy and other drugs

Integrating Biobank data with electronic health record yields personalized pharmacogenetic insights that can spare patients pain – and perhaps save their lives.
Oct. 5, 2022

 

a photo of genetics, which can be used to predict drug reactions.
The Biobank at the Colorado Center of Personalized Medicine, a partnership between UCHealth and the University of Colorado Anschutz Medical Campus, is helping patients avoid adverse reactions to medications – most recently, those that fight cancer. Photo: Getty Images

The Biobank at the Colorado Center for Personalized Medicine is now helping chemotherapy patients avoid a bitter pill.

Since June, the joint University of Colorado Anschutz Medical Campus-UCHealth repository for genetic information has provided data on a particular gene – DPYD – to the UCHealth electronic health record. The addition won’t make a difference for most of the 90,000 (and counting) UCHealth patients who have submitted blood samples to the biobank for DNA analyis. But for some, their survival could hinge on it.

Dr. Christopher Lieu, a UCHealth and CU School of Medicine oncologist, who know uses genetics to help predict his patient's reactions to certain drugs.
Dr. Christopher Lieu

The DPYD gene helps regulate how the body clears two widely used chemotherapy drugs: 5-fluorouracil and capecitabine. About 1,500 UCHealth patients received one of these drugs last year, said Christina Aquilante, a CU Skaggs School of Pharmacy professor and director of pharmacogenomics at the Colorado Center for Personalized Medicine. “These drugs are a backbone treatment for a lot of malignancies – colorectal, pancreatic, and breast cancer among them,” she said.

But those with a faulty DPYD gene may have severe and even deadly reactions to the chemotherapy. Despite this, the genetic testing required to spot a DPYD-gene problem isn’t usually done. That’s changing at UCHealth.

Red flag warning: abnormal DPYD gene

Dr. Christopher Lieu, a UCHealth and CU School of Medicine oncologist, got the first alert identifying a patient with an abnormal DPYD gene. The patient had already received a fluorouracil and had then suffered extreme side effects including mouth sores, diarrhea, and low white blood cell counts. The alert came too late for that round – the treatment had preceded the DPYD rollout – but it helped both Lieu and the patient understand why the reaction had been so bad. It also helped Lieu plan the best postsurgical chemotherapy regimen.

“The information explained to me why they were having the problems they were having,” Lieu said.

The next patient the biobank flags with a DPYD variant will benefit beforehand, he added.

“I think this can be incredibly helpful in terms of knowing who might have a severe reaction to chemotherapy,” he said. “And that helps me as a doctor in knowing where it might be dangerous to give a particular chemotherapy.”

With such foreknowledge, oncologists such as Lieu can go with lower doses or choose alternative chemotherapies. Doing so can not only minimize patient pain but also avoid delays in care that false starts with ill-matched chemotherapies can trigger.

Christina Aquilante, a CU Skaggs School of Pharmacy professor and director of pharmacogenomics at the Colorado Center for Personalized Medicine, who looks at genetics and drug reactions.
Christina Aquilante

“The longer you have cancer, the more likely it is to progress and even spread. If you’re messing around with different chemo regimens, from first-line to second-line to third-line, the greater the chances of not finishing a course that will slow the disease down,” said Dr. David Kao, a UCHealth and Colorado School of Medicine cardiologist who serves as medical director of the Colorado Center for Personalized Medicine. “Slowing chemotherapy down is counterproductive.”

Genetics and drug reactions: more than chemo

Avoiding statins when high cholesterol can starkly elevate heart-attack risk is also counterproductive. But it happens often, Kao says, because of genetic traits that cause statins to trigger muscle pain in some patients.

With other drug interactions, the threat is more imminent.

“There are certain genes where the side effect is death,” Kao said. “For those situations, it is critical to identify at-risk patients even if the abnormal gene is relatively rare, as in the case of DPYD.”

Thanks to pharmacogenetic input from the biobank, physicians can choose different statins or cut the dosage, he says.

So far, the Colorado Center for Personalized Medicine has processes in place to alert doctors of possible patient-drug interactions related to three pharmacogenetic genes: DPYD, SLCO1B1, and CYP2C19, Aquilante says. Those genes affect the metabolism of some 20 medications. They include a range of widely-prescribed medications including statins such as Lipitor and Crestor, antiplatelet medications such as Plavix, proton-pump inhibitors such as Prilosec, and antidepressants like Lexapro and Celexa, she adds.

Expanding knowledge of pharmacogenetic genes, other genetic variants

More pharmacogenetic alerts are on the way, Kao says. Researchers have identified a growing list of pharmacogenetic genes, and it looks like the vast majority of people harbor variations in these genes that may affect how we process particular drugs. The biobank is expanding its portfolio of genomic-testing platforms as well as working on the breadth, quality, and timing of information provided to providers and patients, he says.

Dr. David Kao, a UCHealth and Colorado School of Medicine cardiologist who serves as medical director of the Colorado Center for Personalized Medicine, who looks at genetics and drug reactions.
Dr. David Kao

The biobank’s mandate of bringing personalized or precision medicine into medical care based on patients’ genetic makeup extends well beyond pharmacogenetics. Analyses are being used to identify genetic variants with “significant health implications” that place a patient at risk for health conditions, including certain types of cancer and heart disease, for which early intervention can make a difference.

“Today, we are looking for this type of genetic variation in 78 different genes,” said Kristy Crooks, a UCHealth and CU School of Medicine clinical molecular and cytogeneticist who serves as director of the Colorado Center for Personalized Medicine biobank. “Returning these genetic test results to patients who have consented to receive this information ensures that biobank participants can work with their health care providers to reduce their health risks.”

You can sign up for the biobank. Once you sign in, you will view a video and link to a consent form.

With growing pharmacogenetics capabilities and much more, the medical community’s longstanding aspirations of providing tailored medical treatment down to the molecular level are being realized today.

“Everyone says, ‘It’s the future of medicine,’” Aquilante said. “Well, it’s happening now at UCHealth. It’s happening with the biobank. It’s not science fiction. It’s helping people in really important ways.”

About the author

Todd Neff has written hundreds of stories for University of Colorado Hospital and UCHealth. He covered science and the environment for the Daily Camera in Boulder, Colorado, and has taught narrative nonfiction at the University of Colorado, where he was a Ted Scripps Fellowship recipient in Environmental Journalism. He is author of “A Beard Cut Short,” a biography of a remarkable professor; “The Laser That’s Changing the World,” a history of lidar; and “From Jars to the Stars,” a history of Ball Aerospace.

ADVERTISEMENT