By Kathleen O’Brien, MS, CGC and Trishna Subas, MS, CGC

Better Health

The existence of adverse reactions to medical drugs has been burned into our collective psyche, from the fine print on every drug bottle, to the long list of side effects muttered quickly at the end of drug commercials. Often, we accept that while taking a drug may help you, there is a small risk it may hurt you seriously instead. Instead of simply accepting these risks, there are ways to reduce the risk of adverse reactions to certain drugs by considering a patient’s genetics. Pharmacogenetics (or pharmacogenomics) looks at how genetics influences a person’s response to medications. Let’s look at a cancer treatment, 5-fluorouracil, and see how knowing a patient’s DPYD genotype can reduce the risk of adverse reactions and even save their life.

Why do genes matter when prescribing drugs?
Certain genetic variants (mutations) make some people less likely to benefit from a medication or more likely to have toxic side effects. Certain genes influence the level of enzymes that play a part in how fast or slow certain drugs are metabolized. Knowing someone’s gene status can alert you to some potentially life-threatening adverse drug reactions. Genetic factors are not the only thing influencing medication response, but knowing about genetic differences can provide a more complete clinical picture and personalized treatment.

What is an example? Cancer treatment drug 5-fluorouracil and the gene DPYD
People who are diagnosed with breast cancer, colon cancer, and other cancers with a solid tumor type may be treated with 5-fluorouracil. 5-fluorouracil is processed by an enzyme (dihydropyrimidine dehydrogenase), which is encoded for by the gene DPYD. Certain variants in the DPYD gene decrease or eliminate the enzyme’s function. When an individual who has decreased enzyme function is given the drug 5- fluorouracil, their body does not clear the drug as quickly as other people, and the buildup of the drug can lead to toxic side effects. These side effects include diarrhea, stomatitis, neutropenia, and vomiting, and can be life-threatening.  Over 2 million people a year may be eligible for treatment with this drug and 10-40% of them will experience severe side effects.1. Genetic testing for DPYD can help identify those people who are more likely to experience toxicity and allow for more individualized therapy.

What do you do with this information?
Providers who are thinking of prescribing 5-fluorouracil can order DPYD genetic testing for their patients. Patients with somewhat decreased function may be advised to start on lower doses of the medication, and patients with no function may be advised to avoid the medication entirely. Testing DPYD can lead to a reduction in the number of patients who have serious adverse side effects. Typically, variants that are known to cause decreased enzyme function and are relatively common in the population are tested; however, not all variants that cause decreased function will be detected. If a provider is less familiar with pharmacogenetics or available test options, genetic counselors and pharmacists at Quest Diagnostics are available for consultation.

What will gene–drug testing look like in the future?
Many hospitals and providers currently utilize pharmacogenetic testing to provide more personalized patient care.  Significant gene-drug interactions are being identified more and more frequently and testing is becoming more common.  Quest genetic counselors, or a pharmacist are available to help you with questions about available testing.  It is important to keep in mind that many things influence drug response and pharmacogenetics information is just one piece of a complex puzzle.

For more information about DPYD testing and ordering, healthcare providers can call 1.866.GENE INFO (1.866.436.3463) and speak to our Genomics Client Service Specialists, genetic counselors, or a Quest PharmD.

1.Amstutz U, Henricks LM, Offer SM, Barbarino J, Schellens JHM, Swen JJ, Klein TE, McLeod HL, Caudle KE, Diasio RB, Schwab M. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther. 2018 Feb;103(2):210-216. doi: 10.1002/cpt.911.  PMID: 29152729; PMCID: PMC5760397