DPYD rs1801265: What Your Genotype Means
The rs1801265 variant is a specific genetic change within the DPYD gene, which provides instructions for the enzyme dihydropyrimidine dehydrogenase (DPD). This variant is associated with DPD deficiency, a condition that can lead to severe, life-threatening toxicity when patients are treated with fluoropyrimidine chemotherapy drugs like 5-FU or capecitabine.
What each genotype means
Normal enzyme function
This genotype is assigned normal function by the Clinical Pharmacogenetics Implementation Consortium (CPIC). While some studies have explored potential associations, current evidence does not indicate an altered risk of fluoropyrimidine-related toxicity compared to other genotypes. Always discuss your chemotherapy treatment plan and any concerns about potential side effects with your oncologist or pharmacist.
This is the most common genotype observed across most global populations.
Normal enzyme function
This genotype is assigned normal function by the Clinical Pharmacogenetics Implementation Consortium (CPIC). Research indicates that individuals with this genotype do not have a significantly altered risk of drug toxicity when treated with fluoropyrimidines like 5-fluorouracil. Please consult your healthcare provider to discuss your specific treatment plan and any clinical factors that may influence your medication response.
This genotype is found at varying frequencies globally, though it is less common than the homozygous reference genotype.
Normal enzyme function
This genotype is assigned normal function by the Clinical Pharmacogenetics Implementation Consortium (CPIC). Current evidence suggests that patients with this genotype do not have an altered risk of fluoropyrimidine-induced toxicity compared to those with other genotypes. As with any cancer treatment, you should discuss your medication dosing and potential side effects with your clinical team.
This genotype is observed in various populations, with specific frequencies noted in some indigenous groups, such as the Yanomami and Munduruku in the Brazilian Amazon.
Understanding the rs1801265 Variant
The rs1801265 variant, often referred to in clinical literature as the DPYD*13 allele, is a single nucleotide polymorphism (SNP) located within the DPYD gene. Specifically, this variant involves a change in the DNA sequence that results in an amino acid substitution (p.Ile560Thr) in the resulting protein. This alteration is classified as a non-functional variant, meaning it significantly impairs the ability of the DPD enzyme to perform its normal biological function. Because the DPD enzyme is the primary catalyst for breaking down fluoropyrimidine drugs in the body, the presence of this variant can lead to an accumulation of these medications. When the drug is not cleared from the system at the expected rate, it can reach toxic levels, causing severe adverse reactions in patients undergoing cancer treatment.
The Role of the DPYD Gene
The DPYD gene is located on chromosome 1 and is responsible for encoding the enzyme dihydropyrimidine dehydrogenase (DPD). This enzyme is the rate-limiting step in the catabolism of uracil and thymine, as well as the fluoropyrimidine class of chemotherapy drugs, which includes 5-fluorouracil (5-FU) and its oral prodrug, capecitabine. In a healthy individual, DPD efficiently breaks down these drugs into inactive metabolites, allowing the body to clear them safely. However, when an individual carries variants that reduce or eliminate DPD activity, the drugs remain active in the bloodstream for much longer than intended. This leads to a state known as DPD deficiency. Patients with this deficiency are at a significantly higher risk of experiencing severe, and sometimes fatal, toxicities such as neutropenia, mucositis, and diarrhea when receiving standard doses of fluoropyrimidine-based chemotherapy.
Research and Clinical Evidence
Research into DPYD variants has established them as critical markers in pharmacogenomics. While many variants exist within the DPYD gene, rs1801265 is recognized as a high-impact, albeit rare, contributor to DPD deficiency. Clinical studies and meta-analyses have consistently identified that carriers of deleterious DPYD variants face a substantially elevated risk of treatment-related mortality and severe adverse events compared to non-carriers. The evidence strength for the clinical impact of DPYD variants is robust, leading many oncology guidelines to recommend pre-treatment screening. It is important to note that while the association between DPYD variants and toxicity is well-documented, the clinical presentation can vary between individuals. Because the evidence for specific rare variants like rs1801265 is sometimes categorized as limited in certain populations due to its low frequency, clinicians must interpret genetic results within the broader context of a patient's overall health and treatment plan.
What This Information Means for You
If you or a loved one are considering or currently undergoing treatment with fluoropyrimidine chemotherapy, understanding your DPYD status may be relevant. Genetic testing for DPYD variants is increasingly used to guide personalized dosing strategies, potentially allowing oncologists to reduce the risk of severe toxicity by adjusting medication levels upfront. However, it is vital to understand that this information is not a diagnosis of DPD deficiency, nor does it predict every possible side effect of chemotherapy. You should never make changes to your medication or treatment schedule based on genetic test results without consulting your oncologist or a clinical pharmacist. These professionals are trained to integrate your genetic profile with other clinical factors to determine the safest and most effective therapeutic approach for your specific situation.
How common is this variant?
The rs1801265 variant is rare, with a minor allele frequency of approximately 0.1% across global populations.
Frequently asked questions
What is DPD deficiency?
DPD deficiency is a condition where the body lacks enough of the DPD enzyme to properly break down certain substances, including fluoropyrimidine chemotherapy drugs. This can lead to the buildup of these drugs, causing severe and potentially life-threatening side effects.
Should I get tested for DPYD variants?
Testing for DPYD variants is often recommended for patients scheduled to receive fluoropyrimidine chemotherapy. You should discuss the necessity and implications of this testing with your oncologist to see if it is appropriate for your specific treatment plan.
Does having a DPYD variant mean I cannot have chemotherapy?
Not necessarily. If a patient is found to have a DPYD variant, their medical team may choose to adjust the dosage of the chemotherapy, select an alternative treatment, or monitor the patient more closely to manage the risk of toxicity.
Is rs1801265 the only DPYD variant that matters?
No, there are many known variants in the DPYD gene that can affect enzyme activity. Clinicians often screen for a panel of common variants, including rs1801265, to get a more complete picture of a patient's risk profile.
Sources & further reading
Educational information only, last refreshed 9/29/2026. 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.
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.