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Decoding DPYD: How Genetic Testing Can Reduce Colorectal Cancer Treatment Costs

Lena Voss in Health & Wellness December 2025 • 4 min read.

"A groundbreaking study reveals the impact of DPYD gene variants on fluoropyrimidine toxicity and explores the potential of genetic testing to improve treatment outcomes and manage healthcare expenses."

Colorectal cancer (CRC) treatment often involves fluoropyrimidines, powerful drugs with a significant drawback: unpredictable and sometimes severe toxicity. This toxicity not only diminishes a patient's quality of life and the therapy's effectiveness but also substantially increases healthcare costs. Recognizing the genetic factors influencing drug response is crucial for optimizing treatment strategies and resource allocation.

A critical enzyme in the fluoropyrimidine metabolic pathway is dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. Genetic variations in DPYD can lead to reduced or absent DPD activity, putting carriers at high risk for life-threatening toxicities. Updated guidelines emphasize the importance of identifying these DPYD variants before starting fluoropyrimidine treatment.

While genetic testing for DPYD variants is available, its adoption in routine clinical practice has been slow. A major hurdle is the lack of comprehensive data demonstrating the cost-effectiveness of preemptive DPYD screening. Addressing this gap, a recent study investigated the association between DPYD variants and the costs associated with managing fluoropyrimidine-related toxicities, offering new insights into personalized cancer care.

Unlocking the Link: DPYD Variants and Treatment Costs

The study, led by researchers at the CRO Aviano National Cancer Institute in Italy and the University of North Carolina, examined data from 550 colorectal cancer patients treated with fluoropyrimidine-based chemotherapy. The researchers retrospectively analyzed the patients' DPYD genotypes for several key variants (DPYD2A, DPYD13, DPYDc.2846A>T, and DPYD-HapB3) and tracked the costs associated with managing any toxicities that arose during treatment.

The findings revealed a significant correlation between DPYD variants and treatment costs. Patients with at least one DPYD variant experienced substantially higher toxicity management costs (€2,972, 95%CI €2,456-3,505) compared to those without any variants (€825, 95%CI €785-864). This translates to a nearly fourfold increase in expenses for carriers of DPYD variants. Moreover, these individuals faced a greater risk of needing hospitalization due to toxicity (OR=4.14, 95%CI 1.87-9.14).

Higher Costs: DPYD variant carriers incurred almost four times higher toxicity management costs.
Increased Hospitalization Risk: These patients had a significantly elevated risk of hospitalization.
Significant Economic Burden: Just 6.7% of patients (DPYD carriers) accounted for 20.7% of overall treatment costs.

The study also considered the combined impact of DPYD and UGT1A128 variants in patients receiving fluoropyrimidine/irinotecan. The cost difference between carriers of both DPYD variants and UGT1A128/28 and non-carriers was €2,975, highlighting the potential for even greater cost savings through comprehensive genetic screening.

The Future of Personalized Cancer Care

This research provides a compelling case for incorporating preemptive DPYD screening into routine clinical practice for colorectal cancer patients. By identifying individuals at high risk for fluoropyrimidine-related toxicities, clinicians can adjust treatment regimens, reduce hospitalizations, and ultimately lower healthcare costs. As genetic testing becomes more accessible and affordable, personalized medicine approaches like DPYD screening promise to transform cancer care, improving both patient outcomes and resource utilization.

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Everything You Need To Know

What is DPYD and why is it relevant to colorectal cancer treatment?

DPYD stands for dihydropyrimidine dehydrogenase, an enzyme crucial in the metabolic pathway of fluoropyrimidines, drugs often used in colorectal cancer treatment. Genetic variations in the DPYD gene can impact the activity of the DPD enzyme. Reduced DPD activity, due to these DPYD variants, can lead to increased risk of severe toxicity when patients are treated with fluoropyrimidines. This makes understanding DPYD variants vital for optimizing treatment and minimizing adverse effects.

How do DPYD variants affect the cost of colorectal cancer treatment?

Research has shown a direct correlation between DPYD variants and increased treatment costs. Patients carrying at least one DPYD variant experienced significantly higher costs related to managing the toxic effects of fluoropyrimidine-based chemotherapy. These costs are nearly four times higher compared to patients without any variants, primarily due to the need for additional interventions, increased hospitalizations, and overall more intensive care. Furthermore, the study highlights that a small percentage of patients with DPYD variants account for a significant portion of the total treatment costs.

What are the specific DPYD variants that are of concern in this context?

The study focused on several key DPYD variants: DPYD*2A, DPYD*13, DPYDc.2846A>T, and DPYD-HapB3. These specific variants are known to influence the functionality of the DPD enzyme. Detecting these DPYD variants helps to predict an individual's likelihood of experiencing severe reactions to fluoropyrimidine drugs. Identifying these variants allows for preemptive measures such as dose adjustments or alternative treatments to mitigate potential toxicities, thereby improving treatment outcomes and managing costs.

How can genetic testing for DPYD variants improve colorectal cancer treatment?

Preemptive DPYD screening offers a pathway to personalized medicine in colorectal cancer treatment. By identifying individuals with DPYD variants before starting fluoropyrimidine therapy, clinicians can tailor treatment strategies. This might involve adjusting the drug dosage or selecting alternative chemotherapeutic agents to reduce the risk of severe toxicity. The benefits extend beyond improved patient outcomes; it can also lead to fewer hospitalizations and overall reduced healthcare costs. This approach represents a significant shift toward more effective, safer, and cost-efficient cancer care.

What are the implications of combining DPYD and UGT1A1*28 genetic testing?

The study indicates that the combined impact of DPYD and UGT1A1*28 variants can further influence treatment costs. Patients with both DPYD variants and UGT1A1*28/*28 experienced even higher treatment costs compared to non-carriers. This suggests that comprehensive genetic screening, considering multiple genetic factors, can offer even greater benefits. It provides a more detailed picture of a patient's potential response to treatment and enables a more refined and effective treatment plan. The goal is to enhance patient outcomes and maximize cost savings in colorectal cancer treatment by taking into account multiple genetic variants.