DPYD rs56161402: What Your Genotype Means
The rs56161402 variant, also known as DPYD c.557A>G, is a genetic change in the DPYD gene that can reduce the activity of the DPD enzyme. This reduction may affect how the body processes certain chemotherapy medications, potentially increasing the risk of severe side effects.
What each genotype means
Normal predicted enzyme activity
You carry the most common, reference version of this genetic location. Research suggests this genotype is typically associated with normal DPD enzyme function regarding this specific variant. Please note that other genetic or non-genetic factors may still influence how you process medications; always discuss your treatment plan and any concerns about drug sensitivity with your clinician or pharmacist.
This is the most common genotype across all global populations.
Reduced enzyme activity
You carry one copy of the variant associated with reduced DPD enzyme activity. Scientific literature indicates that individuals with this genotype may have a higher risk of experiencing side effects—such as severe gastrointestinal issues or blood cell count reductions—if treated with fluoropyrimidine chemotherapy. Because evidence for this specific variant is considered limited in some contexts, it is important to discuss these findings with your oncology team or pharmacist to evaluate your individualized risk and treatment options.
Carried by roughly 1–5% of individuals of African ancestry; it is considered very rare or absent in populations of European ancestry.
Significantly reduced enzyme activity
You carry two copies of the variant associated with reduced DPD enzyme activity. Research suggests that this genotype may significantly impair the body's ability to break down fluoropyrimidine medications, substantially increasing the risk of severe drug toxicity. You should share this genetic information with your healthcare provider before starting any fluoropyrimidine-based therapy, as it may be necessary to adjust your dosage or select alternative treatments to ensure your safety.
This genotype is very rare, observed primarily in specific populations of African ancestry.
Understanding the rs56161402 Variant
The rs56161402 variant is a specific single nucleotide polymorphism (SNP) located within the DPYD gene. In genetic nomenclature, this is often referred to as c.557A>G, which describes a change from an adenine (A) to a guanine (G) at a specific position in the gene's DNA sequence. This change results in an amino acid substitution, specifically replacing tyrosine with cysteine at position 186 of the protein (p.Tyr186Cys). Because this alteration occurs in the coding region of the gene, it has the potential to change the structure and function of the resulting protein. Scientists study this variant because it is located in a gene critical for drug metabolism, making it a subject of interest in the field of pharmacogenomics—the study of how genes influence an individual's response to medications.
The Role of the DPYD Gene
The DPYD gene provides instructions for making an enzyme called dihydropyrimidine dehydrogenase (DPD). This enzyme is primarily responsible for breaking down fluoropyrimidines, a class of chemotherapy drugs used to treat various cancers, including colorectal and breast cancer. DPD acts as the rate-limiting step in the metabolism of these drugs, meaning it controls the speed at which the body clears the medication from the system. When DPD activity is normal, the body processes these drugs efficiently. However, if the DPYD gene contains variants that reduce or eliminate DPD enzyme function, the drugs may not be broken down as expected. This can lead to an accumulation of toxic metabolites in the body, which is associated with an increased risk of severe, and sometimes life-threatening, adverse reactions during chemotherapy treatment.
Research and Clinical Evidence
Research into rs56161402 has identified it as a reduced-function variant. Studies have shown that individuals carrying this variant may have decreased DPD enzymatic activity compared to those without it. In the context of cancer treatment, this is clinically significant because patients with reduced DPD activity are more susceptible to severe fluoropyrimidine-related toxicity. While the evidence linking this specific variant to toxicity is recognized, it is often categorized as having limited or evolving clinical strength compared to more well-studied DPYD variants like *2A. Because of this, clinical guidelines continue to refine how this information is used to guide dosing. It is essential to understand that genetic status is only one factor in drug response; clinicians consider many variables, including overall health and other medications, when determining a treatment plan.
Population Frequency
The frequency of the rs56161402 variant varies significantly across different ancestral groups. Research indicates that this variant is more commonly observed in individuals of African ancestry, with a minor allele frequency (MAF) typically reported between 3% and 5%. In contrast, the variant is considered rare in populations of European ancestry. These differences highlight the importance of considering genetic diversity in pharmacogenetic research and clinical implementation. Because the variant is more prevalent in specific populations, screening programs in diverse communities are increasingly focusing on this marker to ensure that personalized medicine approaches are equitable and effective for all patients, regardless of their ancestral background.
What This Information Means for You
If you have received information about your rs56161402 status, it is important to view it in the proper context. This variant is a tool for clinicians to help predict potential drug responses, but it is not a diagnosis of a disease or a guarantee of how you will react to a medication. You should never make changes to your prescribed medications or treatment plans based on genetic test results without consulting your healthcare provider. If you are scheduled for treatment with fluoropyrimidines, discuss your genetic profile with your oncologist or a clinical pharmacist. They are the best resources to interpret these results in the context of your specific medical history and to determine if a dose adjustment or alternative therapy is appropriate for your care.
How common is this variant?
The rs56161402 variant has a minor allele frequency of approximately 3-5% in individuals of African ancestry, while it remains rare in European populations.
Frequently asked questions
What is DPD deficiency?
DPD deficiency is a condition where the body lacks enough of the dihydropyrimidine dehydrogenase enzyme. This enzyme is necessary to break down fluoropyrimidine chemotherapy drugs, and a deficiency can lead to toxic drug accumulation.
Does having the rs56161402 variant mean I cannot have chemotherapy?
No, it does not necessarily mean you cannot have chemotherapy. It simply means your doctor may need to adjust your dosage or monitor you more closely to prevent severe side effects.
Is rs56161402 the only variant that affects fluoropyrimidine toxicity?
No, there are several other variants in the DPYD gene, such as *2A and c.2846A>T, that are also known to affect DPD activity. Clinicians often look at a panel of variants to get a complete picture of a patient's risk.
Should I get tested for DPYD variants?
Whether you should be tested depends on your specific treatment plan and medical history. You should discuss the necessity and potential benefits of pharmacogenetic testing with your oncologist.
Sources & further reading
Educational information only, last refreshed 9/25/2026. 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.
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.