DPYD rs28365042: What Your Genotype Means
The rs28365042 variant is a genetic change located within the DPYD gene, which provides instructions for making the dihydropyrimidine dehydrogenase (DPD) enzyme. This variant is studied in the context of pharmacogenomics due to its potential association with altered DPD activity and the risk of toxicity during treatment with fluoropyrimidine-based chemotherapy.
What each genotype means
Typical enzyme activity
This genotype represents the most common form of the DPYD gene. Individuals with this profile are generally expected to have standard dihydropyrimidine dehydrogenase (DPD) enzyme activity. Please discuss any planned chemotherapy with your clinician to ensure appropriate treatment planning.
This is the most common genotype found in the vast majority of the global population.
Potential reduced enzyme activity
This genotype includes one copy of the variant allele, which has been associated with decreased DPD enzyme activity in some research contexts. Because this variant is rare, the clinical impact for an individual carrier is not fully established and may vary. You should discuss this result with your oncologist or a pharmacist before starting fluoropyrimidine-based chemotherapy.
This genotype is rare and observed at very low frequencies across most studied populations.
Likely reduced enzyme activity
This genotype indicates the presence of two copies of the variant allele, which may be linked to a more significant reduction in DPD enzyme activity. Research suggests that reduced DPD activity can increase the risk of severe side effects when taking fluoropyrimidine medications. It is essential to consult with your healthcare provider to review your treatment options and potential dosage adjustments.
This genotype is extremely rare in the general population.
Understanding the DPYD Gene and rs28365042
The DPYD gene is responsible for producing the enzyme dihydropyrimidine dehydrogenase (DPD). This enzyme is the rate-limiting step in the metabolism of fluoropyrimidines, a class of chemotherapy drugs that includes 5-fluorouracil (5-FU) and capecitabine. When DPD function is reduced or absent, these drugs can accumulate to toxic levels in the body, leading to severe adverse reactions. The variant rs28365042 is a specific single nucleotide polymorphism (SNP) located within the DPYD gene sequence. Researchers track such variants to understand how individual genetic differences influence the body's ability to process these medications. While some DPYD variants are well-established as markers for DPD deficiency, rs28365042 is categorized as having limited evidence regarding its clinical impact. It is one of many variations identified in the DPYD gene that scientists continue to investigate to better predict patient responses to cancer therapies.
Research and Clinical Evidence
Current research into DPYD variants focuses on identifying genetic markers that can predict severe toxicity in patients undergoing fluoropyrimidine chemotherapy. While certain variants, such as those linked to DPD deficiency, have strong evidence supporting their role in treatment-related mortality, the evidence for rs28365042 remains limited. Studies often analyze how specific amino acid substitutions or intronic changes affect the conformation and enzymatic clearance of DPD. Because DPYD is highly polymorphic, researchers are working to distinguish between variants that significantly impair enzyme function and those that have a neutral or negligible effect. For rs28365042, clinical data is not as robust as it is for major risk alleles like DPYD*2A. Consequently, it is not currently a standard component of routine clinical screening panels. Ongoing studies continue to evaluate whether this variant, either alone or in combination with other genetic factors, contributes to the inter-individual variability observed in chemotherapy outcomes.
Population Frequency and Interpretation
The rs28365042 variant is considered rare across most global populations. Genetic frequency can vary significantly depending on ancestral background, and researchers often find that variants identified in one population may not be present or may have different clinical implications in another. Because this variant is rare, large-scale genomic studies are required to accurately estimate its frequency and its potential association with drug metabolism. It is important to note that the presence of a rare variant does not automatically imply a clinical risk. Many genetic variations are benign and do not affect protein function. When interpreting genomic data, scientists look for consistent patterns across large cohorts to determine if a variant is truly pathogenic. For rare variants like rs28365042, the lack of widespread clinical data means that its functional significance remains an area of active scientific inquiry rather than a settled clinical fact.
Managing Your Genetic Information
If you have received information about your DPYD genotype, it is essential to understand that this data is for educational purposes and should not be used to make medical decisions independently. Pharmacogenomic testing is a complex field, and the clinical relevance of any single variant must be interpreted by a qualified healthcare professional, such as an oncologist or a clinical pharmacist. You should never alter your medication dosage or treatment plan based on genetic test results without consulting your clinical team. If you are scheduled for chemotherapy, discuss your genetic profile with your doctor. They can provide context on whether specific testing is recommended for your treatment plan and how your results might influence clinical decision-making. Your healthcare provider is the best resource for integrating genetic information into your overall care strategy, ensuring that any adjustments to therapy are based on established clinical guidelines and your specific health history.
How common is this variant?
The rs28365042 variant is classified as rare in the general population, with specific frequency data varying by ancestral group.
Frequently asked questions
What is the DPYD gene?
The DPYD gene provides instructions for making the enzyme dihydropyrimidine dehydrogenase (DPD). This enzyme is essential for breaking down fluoropyrimidine chemotherapy drugs in the body.
Can I use this information to change my chemotherapy dose?
No. You must never change your medication dosage based on genetic information without consulting your oncologist or pharmacist. Only a medical professional can determine if a dose adjustment is safe and appropriate for you.
Is rs28365042 a known cause of chemotherapy toxicity?
The evidence for rs28365042 is currently limited. While other DPYD variants are well-established markers for toxicity, more research is needed to confirm the clinical impact of this specific variant.
Should I get tested for DPYD variants?
Whether you should undergo pharmacogenomic testing depends on your specific treatment plan and medical history. Discuss the potential benefits and limitations of such testing with your healthcare provider.
Sources & further reading
Educational information only, last refreshed 10/3/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A rare but high-risk variant for severe adverse reactions to chemotherapy.
Dramatically increases risk of life-threatening toxicity from 5-FU chemotherapy.
Associated with significantly reduced metabolism of fluoropyrimidine drugs.
Defines the non-functional DPYD*7 variant (p.Leu311Phe) that severely impairs pyrimidine degradation, predisposing carriers to fluoropyrimidine neurotoxicity and cytopenias.
Constitutes the non-functional DPYD*13 variant (p.Ile560Thr), associated with severe dihydropyrimidine dehydrogenase deficiency and life-threatening toxicity from fluoropyrimidines (5-FU, capecitabine).
Also designated as DPYD c.557A>G (p.Tyr186Cys), this variant significantly decreases dihydropyrimidine dehydrogenase activity and predisposes patients to severe fluoropyrimidine toxicity.