DPYD rs75527207: Understanding Chemotherapy Response Risks
The rs75527207 variant is a genetic marker located within the DPYD gene, which is responsible for producing the enzyme dihydropyrimidine dehydrogenase (DPD). This variant is studied for its potential association with severe adverse reactions in patients undergoing treatment with fluoropyrimidine-based chemotherapy drugs.
What each genotype means
Normal enzyme activity
This genotype is considered the wild-type or normal sequence for this position in the DPYD gene. Individuals with this profile are expected to have standard dihydropyrimidine dehydrogenase (DPD) enzyme activity, which is responsible for breaking down fluoropyrimidine chemotherapy drugs. Always consult with your oncologist or pharmacist regarding any planned chemotherapy treatments.
This is the most common genotype found in the vast majority of the global population.
Reduced enzyme activity
This genotype indicates the presence of one copy of the variant allele, which may be associated with reduced DPD enzyme activity. Reduced activity can lead to an accumulation of fluoropyrimidine drugs in the body, potentially increasing the risk of severe or fatal toxicity during chemotherapy. Please discuss this result with your healthcare provider or a clinical pharmacist before starting any fluoropyrimidine-based treatment.
This genotype is rare, occurring in less than 0.1% of the global population.
Significantly reduced enzyme activity
This genotype indicates the presence of two copies of the variant allele, which is strongly associated with a profound deficiency in DPD enzyme activity. Individuals with this profile are at a very high risk for severe, life-threatening adverse reactions if treated with standard doses of fluoropyrimidine chemotherapy. It is critical to discuss this finding with your medical team, as alternative treatment strategies or significant dose adjustments are typically required.
This genotype is extremely rare, found in a negligible fraction of the global population.
What is the DPYD Gene?
The DPYD gene provides the essential instructions for the body to create the enzyme dihydropyrimidine dehydrogenase (DPD). This enzyme plays a critical role in the metabolic breakdown of uracil and thymine, which are natural molecules known as pyrimidines. By breaking these down, the body maintains a healthy balance of these nucleotides. Beyond its natural function, DPD is also responsible for metabolizing certain chemotherapy medications, specifically fluoropyrimidines like 5-fluorouracil and capecitabine. When the DPYD gene contains variants that reduce or eliminate the activity of the DPD enzyme, these drugs can accumulate to toxic levels in the bloodstream. This accumulation is what leads to the severe adverse reactions sometimes observed in patients receiving these specific cancer treatments. Understanding the function of this gene is a cornerstone of pharmacogenomics, the study of how genes influence an individual's response to medications.
Understanding the rs75527207 Variant
The rs75527207 variant is a specific change in the DNA sequence within the DPYD gene. In the context of clinical research, scientists investigate such variants to determine if they alter the efficiency of the DPD enzyme. While some DPYD variants are well-established as high-risk markers for chemotherapy toxicity, rs75527207 is categorized as a rare variant. Research into rare variants is ongoing, as their individual impact on enzyme function can be difficult to predict compared to more common, well-studied mutations. Current scientific literature emphasizes that the presence of rare variants in DPYD can contribute to a 'burden' of genetic risk, potentially predisposing individuals to adverse events. Because this variant is rare, clinical evidence regarding its specific effect size is still evolving. Researchers often use computational modeling and patient-specific metabolic testing to better understand how these rare changes influence the body's ability to process chemotherapy drugs safely.
Clinical Significance and Evidence
The evidence linking specific DPYD variants to chemotherapy toxicity is considered moderate to strong for well-known markers, but it remains a complex area for rarer variants like rs75527207. Clinical guidelines currently recommend screening for several major DPYD variants before starting fluoropyrimidine therapy to prevent severe toxicity. However, because some patients experience adverse reactions despite testing negative for these common markers, researchers are actively investigating the role of rarer variants. It is important to note that genetic testing is only one tool used by clinicians. Other methods, such as measuring the ratio of uracil to dihydrouracil in the plasma, are also used to assess DPD activity directly. If you or a family member are scheduled for chemotherapy, it is essential to discuss your genetic profile and any concerns about drug sensitivity with your oncologist or a clinical pharmacist. They are the only ones qualified to interpret these results in the context of your specific treatment plan.
What You Can Do With This Information
Genetic information regarding DPYD variants should be treated as a starting point for a conversation with your healthcare provider, not as a standalone medical diagnosis. If you have received a report indicating you carry the rs75527207 variant, do not make any changes to your medication or treatment schedule without professional guidance. This information is most valuable when shared with your medical team, who can weigh it against your clinical history, the type of chemotherapy being considered, and other diagnostic tests. Because the science of pharmacogenomics is rapidly advancing, your doctor may have access to the most current clinical guidelines for managing patients with specific DPYD profiles. Remember that having a variant does not guarantee a specific outcome, and many factors beyond genetics influence how a person responds to treatment. Always prioritize direct communication with your oncology team to ensure your care is personalized, safe, and based on the most accurate clinical data available.
How common is this variant?
The rs75527207 variant is rare, with a global population frequency of less than 0.1%.
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 specific chemotherapy drugs. This can lead to the accumulation of these drugs in the body, causing severe and potentially life-threatening side effects.
Does having a DPYD variant mean I will have a bad reaction to chemotherapy?
Not necessarily. While certain DPYD variants are associated with an increased risk of toxicity, many factors influence how a person responds to chemotherapy. A genetic variant is just one piece of the puzzle that your doctor uses to assess your individual risk.
Should I get tested for DPYD variants before starting cancer treatment?
Clinical guidelines recommend testing for specific, well-established DPYD variants before starting fluoropyrimidine chemotherapy. You should discuss the necessity and benefits of this testing with your oncologist to determine if it is appropriate for your specific treatment plan.
Can I change my DPYD genotype?
No, your genotype is determined by the DNA you inherited from your parents and cannot be changed. However, knowing your genetic profile allows your healthcare team to adjust your treatment plan, such as modifying drug dosages, to improve safety.
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.