DPYD rs3957357: What Your Genotype Means
The rs3957357 variant is a genetic marker located within the DPYD gene, which provides instructions for the dihydropyrimidine dehydrogenase (DPD) enzyme. This variant is studied in pharmacogenomics because it is associated with reduced enzyme activity, which can influence how a patient processes certain chemotherapy medications.
What each genotype means
Typical enzyme expression
You carry two copies of the common reference allele at this regulatory site. Research indicates this genotype is typically associated with baseline levels of dihydropyrimidine dehydrogenase (DPD) expression and conventional fluoropyrimidine metabolism. If you are prescribed fluorouracil or capecitabine chemotherapy, always discuss your comprehensive pharmacogenomic profile and dosing considerations with your oncologist or pharmacist.
Carried by approximately 55% to 65% of individuals of European descent, but less frequent in African populations where the alternate allele is more prevalent.
Modestly reduced enzyme expression
You carry one copy of the regulatory variant allele, which has been linked in preliminary studies to altered DPYD expression and potentially lower clearance of fluoropyrimidine drugs. Because current published evidence for this specific variant is limited and not yet formally integrated into standard CPIC dosing guidelines, its clinical effect remains uncertain. If you are undergoing or planning fluorouracil or capecitabine chemotherapy, discuss full DPYD panel testing and personalized dosing with your clinician or pharmacist.
Carried by roughly 30% to 40% of people of European ancestry and up to 45% of individuals of African descent.
Decreased enzyme expression
You carry two copies of the regulatory variant allele associated with lower DPD expression and increased systemic exposure to fluoropyrimidine-based chemotherapies. While preliminary studies associate this genotype with an elevated risk of severe drug-related toxicities, the evidence remains limited compared to core clinical DPYD alleles such as *2A. If you are prescribed fluorouracil or capecitabine, it is essential to consult your oncologist or clinical pharmacologist regarding comprehensive DPYD status and toxicity monitoring.
Carried by approximately 3% to 6% of European populations and roughly 10% to 16% of African populations.
Understanding the DPYD Gene and rs3957357
The DPYD gene is responsible for producing the dihydropyrimidine dehydrogenase (DPD) enzyme. This enzyme plays a critical role in the body by breaking down uracil and thymine, which are natural building blocks of DNA. Crucially, this same enzyme is responsible for metabolizing fluoropyrimidine-based drugs, such as 5-fluorouracil and capecitabine, which are commonly used to treat various cancers. The variant rs3957357 is an intronic change, meaning it sits in a non-coding region of the gene. While it does not change the protein sequence directly, research indicates it serves as a marker for altered DPD enzyme function. When DPD activity is reduced, these chemotherapy drugs may not be cleared from the body as efficiently as expected, potentially leading to higher concentrations of the medication in the bloodstream.
Research and Clinical Associations
In the field of pharmacogenomics, rs3957357 is recognized as a marker associated with the risk of severe toxicity during treatment with fluoropyrimidine-based chemotherapies. When patients have reduced DPD activity, they are at an increased risk of experiencing adverse reactions, which can range from gastrointestinal distress to more severe, life-threatening complications. Clinical guidelines from organizations like the Clinical Pharmacogenetics Implementation Consortium (CPIC) emphasize the importance of DPYD testing to guide dosing strategies. The evidence for DPYD variants as predictors of toxicity is considered strong, leading many clinical centers to implement prospective screening. However, the predictive value of any single variant can vary, and not every individual with a specific genotype will experience the same clinical outcome. It is essential to view this information as one piece of a larger clinical puzzle that includes patient history and therapeutic drug monitoring.
What This Information Means for You
If you have received information about your DPYD genotype, it is important to understand that this data is intended to support clinical decision-making, not to provide a diagnosis or dictate treatment on its own. Pharmacogenomic testing helps clinicians identify patients who might benefit from an initial dose reduction to improve safety and minimize the risk of severe side effects. If you are scheduled for chemotherapy, you should discuss your genetic results with your oncologist or a clinical pharmacist. They are the only professionals qualified to interpret these results in the context of your specific treatment plan, cancer type, and overall health. Never make changes to your medication regimen based on genetic reports without direct guidance from your medical team. They may use your genotype to adjust your starting dose or implement closer monitoring during your treatment cycles.
How common is this variant?
The rs3957357 variant is found in approximately 1-5% of European populations, though frequencies can vary across different global ancestries.
Frequently asked questions
What is the DPYD gene?
The DPYD gene provides instructions for making the DPD enzyme, which breaks down certain substances in the body, including specific chemotherapy drugs like 5-fluorouracil.
How does rs3957357 affect chemotherapy?
This variant is a marker for reduced DPD enzyme activity. If the enzyme is less active, the body may not break down chemotherapy drugs properly, increasing the risk of severe side effects.
Should I get tested for DPYD variants?
Testing is often recommended for patients before starting fluoropyrimidine-based chemotherapy. You should discuss the necessity and implications of this test with your oncologist.
Does having a variant mean I cannot have chemotherapy?
No, having a variant does not necessarily mean you cannot receive treatment. It often means your doctor may adjust your starting dose or monitor you more closely to ensure your safety.
Sources & further reading
Educational information only, last refreshed 10/6/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.
A synonymous variant in exon 11 (c.1236G>A) that is in high linkage disequilibrium with the causal intronic variant c.1129-5923C>G (rs75017182), which defines the HapB3 haplotype associated with reduced DPYD activity and fluoropyrimidine toxicity.