DPYD rs67376798: What Your Genotype Means for Drug Metabolism
The rs67376798 variant is a specific genetic change in the DPYD gene associated with decreased activity of the dihydropyrimidine dehydrogenase enzyme. This enzyme is responsible for breaking down fluoropyrimidine drugs, and individuals with this variant may have an increased risk of experiencing severe drug toxicity.
What each genotype means
Normal enzyme activity
This is the most common genotype and is typically associated with normal function of the DPD enzyme. Individuals with this genotype are generally expected to metabolize fluoropyrimidine drugs at a standard rate, though other genetic and clinical factors can still influence drug response. Always discuss your medication plan and any concerns about potential side effects with your healthcare provider.
This is the most common genotype found in the vast majority of the global population.
Reduced enzyme activity
This genotype, also referred to as carrying the c.2846A>T or p.Asp949Val variant, is associated with reduced DPD enzyme activity. Research indicates that individuals with this genotype may have an increased risk of experiencing drug toxicity when treated with fluoropyrimidine-based chemotherapies like fluorouracil, capecitabine, or tegafur. Please consult your oncologist or pharmacist to discuss appropriate dosing strategies or alternative treatment options.
This genotype is rare, occurring in less than 1% of the global population.
Significantly reduced enzyme activity
This genotype is associated with a more pronounced reduction in DPD enzyme function compared to the A/T genotype. Carrying two copies of this variant significantly increases the risk of severe or potentially fatal drug toxicity when receiving fluoropyrimidine medications. It is critical to discuss this genetic finding with your medical team before starting any treatment involving these drugs, as they may need to avoid these medications or adjust dosages significantly.
This genotype is very rare, found in a very small fraction of the global population.
Understanding the rs67376798 Variant
The rs67376798 variant, often referred to in clinical literature as c.2846A>T or p.Asp949Val, is a single nucleotide polymorphism located within the DPYD gene. Specifically, this variant sits in coding exon 22 of the gene. In genetics, a SNP represents a variation at a single position in the DNA sequence. For rs67376798, the substitution of an adenine (A) for a thymine (T) can alter the structure of the resulting protein. This specific change is recognized by researchers and clinicians as a marker for reduced enzyme function. Because the DPYD gene provides instructions for making the dihydropyrimidine dehydrogenase (DPD) enzyme, changes in this gene can directly impact how the body processes certain medications, particularly those used in cancer treatment.
The Role of the DPYD Gene
The DPYD gene is essential for the body's ability to metabolize fluoropyrimidines, a class of chemotherapy drugs that includes 5-fluorouracil (5-FU), capecitabine, and tegafur. These drugs are commonly used to treat various types of cancer. The DPD enzyme acts as a metabolic gatekeeper, breaking down these drugs into inactive compounds so they can be safely cleared from the body. When the DPYD gene functions normally, the drug is metabolized at an expected rate. However, if a person carries variants that reduce or eliminate DPD enzyme activity, the drug may accumulate in the bloodstream to toxic levels. This accumulation can lead to severe, and in some cases life-threatening, side effects, such as gastrointestinal distress, bone marrow suppression, and neurotoxicity.
Research and Clinical Evidence
The association between rs67376798 and fluoropyrimidine toxicity is supported by moderate to strong evidence in the field of pharmacogenetics. Clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG), identify this variant as a factor that can lead to decreased DPD activity. Research indicates that individuals carrying this variant may be classified as intermediate metabolizers. Because of this, medical organizations often recommend that clinicians consider DPYD testing before initiating treatment with fluoropyrimidines. While the evidence is robust enough to influence clinical guidelines, it is important to note that individual responses to medication are complex and can be influenced by other genetic and non-genetic factors. Always consult with your oncologist or pharmacist regarding how your specific genetic profile might influence your treatment plan.
What You Can and Cannot Do
If you have received information about your DPYD status, it is vital to understand the limitations of this data. Genetic testing for rs67376798 is a tool for clinical decision-making, not a diagnosis in itself. You cannot use this information to self-diagnose or make changes to your prescribed medication regimen. If you are currently undergoing or planning to undergo chemotherapy, share your genetic test results with your healthcare provider. They are the only ones qualified to interpret these results in the context of your overall health and to adjust your dosage or select alternative therapies if necessary. Never stop or alter your medication based on genetic reports without professional medical guidance. This information is intended to facilitate a conversation with your clinical team to ensure your treatment is as safe and effective as possible.
How common is this variant?
The rs67376798 variant is relatively rare, occurring in less than 1% of the global population. Its frequency can vary across different ancestral groups, and it is typically identified through targeted pharmacogenetic screening.
Frequently asked questions
What is the DPYD gene?
The DPYD gene provides the instructions for the body to produce the dihydropyrimidine dehydrogenase (DPD) enzyme. This enzyme is responsible for breaking down fluoropyrimidine chemotherapy drugs.
Does having the rs67376798 variant mean I have cancer?
No. This variant is a genetic marker related to how your body processes certain medications. It is not a diagnostic test for cancer or any other disease.
Should I get tested for DPYD variants?
DPYD testing is often recommended by clinical guidelines for patients who are about to start fluoropyrimidine-based chemotherapy. You should discuss the necessity and relevance of this testing with your oncologist.
Can I change my chemotherapy dose based on this result?
No. You should never change your medication dosage on your own. Any adjustments to chemotherapy must be made exclusively by your healthcare provider based on your clinical status and genetic information.
Sources & further reading
Educational information only, last refreshed 10/2/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This intronic variant is a marker for reduced DPYD enzyme activity, increasing the risk of severe toxicity from fluoropyrimidine-based chemotherapies.
This variant is linked to decreased dihydropyrimidine dehydrogenase activity, increasing the risk of severe toxicity during fluoropyrimidine chemotherapy.
Defines the DPYD*7 variant (p.Leu311Phe) associated with impaired pyrimidine metabolism and potential fluoropyrimidine toxicity.
Constitutes the DPYD*13 variant (p.Ile560Thr), associated with significantly reduced DPYD enzyme activity and increased risk of severe fluoropyrimidine toxicity.
Also designated as DPYD c.557A>G (p.Tyr186Cys), this variant significantly decreases dihydropyrimidine dehydrogenase activity and predisposes patients to severe fluoropyrimidine toxicity.
Causes the c.2846A>T (p.Asp949Val) missense change in DPYD, associated with reduced enzyme activity and increased risk of fluoropyrimidine-associated toxicity.