DPYD rs3918290: Understanding Fluoropyrimidine Toxicity Risk
The rs3918290 variant is a specific genetic change in the DPYD gene that results in a non-functional enzyme. It is clinically significant because it is strongly associated with an increased risk of severe, life-threatening toxicity in patients receiving fluoropyrimidine-based chemotherapy, such as 5-fluorouracil.
What each genotype means
Normal enzyme activity
This is the most common genotype and is considered the reference or wild-type sequence. Individuals with this genotype do not carry the specific DPYD*2A variant associated with increased fluoropyrimidine toxicity. Please discuss all chemotherapy treatment plans and potential side effects with your oncologist.
Carried by the vast majority of the population across all ancestries.
Reduced enzyme activity
This genotype indicates you carry one copy of the DPYD*2A variant, which is associated with reduced activity of the DPD enzyme. This may impair your body's ability to break down fluoropyrimidine chemotherapy drugs like 5-FU, potentially increasing the risk of severe side effects. You should discuss this genetic finding with your clinician or pharmacist before starting any treatment involving these medications.
This genotype is rare, typically found in approximately 1% of European populations, though frequencies vary by ancestry.
Significantly reduced enzyme activity
This genotype indicates you carry two copies of the DPYD*2A variant, which is linked to a profound deficiency in DPD enzyme activity. This significantly increases the risk of life-threatening toxicity when treated with fluoropyrimidine chemotherapy drugs. It is critical to inform your healthcare team of this result so they can consider alternative therapies or adjusted dosing strategies.
This genotype is extremely rare in the general population.
Significantly reduced enzyme activity
This genotype represents an alternative notation for the risk-associated variant (often referred to as the A allele in some databases) that results in DPD enzyme deficiency. Carrying this genotype is associated with a high risk of severe toxicity from fluoropyrimidine chemotherapy. Please ensure your oncology team is aware of this genetic profile to guide safe medication management.
This genotype is extremely rare in the general population.
What is the rs3918290 Variant?
The rs3918290 variant, often referred to in clinical literature as DPYD*2A, is a single nucleotide polymorphism located within the DPYD gene. Specifically, it involves a G-to-A transition at the splice donor site of intron 14. This genetic alteration is highly consequential because it disrupts the normal processing of messenger RNA, leading to the skipping of exon 14 during protein synthesis. The resulting protein is truncated and lacks the necessary enzymatic activity to function correctly. Because this variant sits at a critical junction for gene expression, it is classified as a loss-of-function allele. In clinical genetics, identifying this variant is a priority because it serves as a predictive marker for how an individual's body might process certain medications, particularly those that rely on the DPYD enzyme for breakdown and clearance from the system.
The Role of the DPYD Gene
The DPYD gene provides instructions for creating the enzyme dihydropyrimidine dehydrogenase (DPD). This enzyme is the rate-limiting step in the catabolism, or breakdown, of uracil and thymine, which are natural components of our cells. More importantly, DPD is responsible for breaking down fluoropyrimidines, a class of chemotherapy drugs that includes 5-fluorouracil (5-FU) and capecitabine. When a patient receives these drugs, the DPD enzyme normally converts the active medication into inactive metabolites, allowing the body to clear the drug safely. If the DPYD gene contains variants that reduce or eliminate DPD activity, the chemotherapy drugs can accumulate to toxic levels in the bloodstream. This accumulation leads to severe side effects, as the body is unable to process the medication at the intended rate, potentially causing damage to healthy tissues.
Research and Clinical Associations
Research consistently demonstrates a strong association between the rs3918290 variant and adverse drug reactions. Clinical studies have shown that individuals carrying this variant have significantly reduced DPD enzyme activity compared to those without it. When these individuals are treated with standard doses of 5-fluorouracil, they are at a much higher risk of experiencing grade 3 or greater toxicity, which can include severe gastrointestinal distress, bone marrow suppression, and neurotoxicity. The evidence for this association is robust, leading major pharmacogenetic organizations like the Clinical Pharmacogenetics Implementation Consortium (CPIC) to develop specific dosing guidelines. These guidelines suggest that clinicians should consider dose reductions or alternative therapies for patients identified as carriers of this variant to prevent life-threatening complications. The strength of this evidence has made rs3918290 a standard marker for pre-treatment screening in many oncology settings.
What You Can and Cannot Do
Understanding your genetic status regarding rs3918290 is a powerful tool for personalized medicine, but it must be used in the right context. If you have received genetic testing results indicating you carry this variant, it is essential that you share this information with your oncologist or pharmacist before starting any chemotherapy regimen. This information allows your medical team to adjust your treatment plan, potentially by lowering the dose or selecting a different medication, to ensure your safety. However, you should never use this information to make independent medical decisions or to diagnose yourself. Genetic testing for drug response is complex, and clinical decisions must always be made by qualified healthcare professionals who can interpret your results alongside your overall health history, current medications, and the specific requirements of your treatment plan.
How common is this variant?
The rs3918290 variant is relatively rare, with a carrier frequency of approximately 1% to 1.2% in European populations.
Frequently asked questions
Is rs3918290 the only variant that affects 5-FU toxicity?
No, there are several other variants in the DPYD gene, such as DPYD*13 and the HapB3 haplotype, that can also affect DPD enzyme activity. Clinicians often screen for a panel of these variants to get a more complete picture of a patient's risk.
Does having the G/A genotype mean I cannot receive chemotherapy?
Not necessarily. Having the variant does not mean you cannot be treated, but it does mean your medical team needs to be aware of your genotype to adjust your dosage or choose a safer alternative to prevent toxicity.
Should everyone get tested for DPYD variants?
Pre-treatment testing is increasingly common and even mandated in some regions for patients scheduled to receive fluoropyrimidine chemotherapy. You should discuss the necessity and benefits of this testing with your oncologist.
Where can I find more information about DPYD guidelines?
The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides peer-reviewed, evidence-based guidelines for DPYD and fluoropyrimidine dosing. These resources are designed for healthcare providers but are publicly available online.
Sources & further reading
Educational information only, last refreshed 10/8/2026. 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.