What you carry at this position in your DNA and what research says about it.
Chemotherapy Toxicity Risk: 8/10 evidence, 10 publications.
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Sample genotype (not yours): T/T
Typical Chemotherapy Toxicity Risk
Normal dihydropyrimidine dehydrogenase enzyme activity is expected. The risk of experiencing severe toxicity if treated with fluorouracil or capecitabine remains at the typical baseline level.
What this genotype means: Normal metabolism of fluoropyrimidine drugs; Typical risk of chemotherapy side effects.
Sample genotype (not yours): C/C
Elevated Chemotherapy Toxicity Risk
Significantly reduced dihydropyrimidine dehydrogenase activity is associated with this genetic profile. This increases the risk of severe toxicity from fluorouracil or capecitabine.
What this genotype means: Significantly slower breakdown of fluoropyrimidine drugs; High risk of severe chemotherapy side effects.
Sample genotype (not yours): T/C
Increased Chemotherapy Toxicity Risk
Reduced dihydropyrimidine dehydrogenase activity is associated with this genetic profile. This may increase the risk of severe side effects if prescribed fluorouracil or capecitabine.
What this genotype means: Slower breakdown of fluoropyrimidine drugs; Higher risk of severe chemotherapy side effects.
Gene function and biological role
Gene Function: The DPYD gene encodes dihydropyrimidine dehydrogenase, an enzyme that plays a critical role in breaking down pyrimidines [1]. This enzyme is the rate-limiting step in the metabolism of uracil and thymine, as well as fluoropyrimidine chemotherapy drugs [1] [2]. When DPYD activity is reduced, these chemotherapy drugs can accumulate to toxic levels in the body [2]. This can lead to severe, sometimes life-threatening side effects during cancer treatment [2] [3]. Genetic variations in this gene are the primary cause of dihydropyrimidine dehydrogenase deficiency [3].
Variant Impact: The rs2297595 variant is a missense mutation in the DPYD gene that results in the replacement of the amino acid methionine with valine at position 166 of the protein [4]. This specific change, often referred to as p.Met166Val, can alter the stability or activity of the dihydropyrimidine dehydrogenase enzyme [4] [2]. While some clinical guidelines classify this variant as having normal function, several clinical studies have linked it to an increased risk of severe toxicity when patients are treated with fluoropyrimidine-based chemotherapies [2] [1]. The variant is relatively common in populations of European and Middle Eastern ancestry [4].
Key Insight: Although some clinical databases classify this variant as having normal function, multiple clinical studies suggest it significantly increases the risk of severe side effects from common chemotherapy drugs.
Location: DPYD. Chromosome 1 · 1p21.3 · 97.7 Mb
Estimated prevalence by population
Global 84.8%; European 80.8%; African 93.3%; East Asian 96.8%; South Asian 85.9%; Americas 87.1%; Ashkenazi 83.9%; Finnish 67.9%; Middle Eastern 79.4%; Amish 77.1%.
Estimated TT genotype frequency.
Global 14.4%; European 18.2%; African 6.6%; East Asian 3.2%; South Asian 13.6%; Americas 12.4%; Ashkenazi 15.4%; Finnish 29.0%; Middle Eastern 19.4%; Amish 21.4%.
Estimated TC genotype frequency.
Global 0.8%; European 1.0%; African 0.1%; East Asian < 0.1%; South Asian 0.5%; Americas 0.4%; Ashkenazi 0.7%; Finnish 3.1%; Middle Eastern 1.2%; Amish 1.5%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Pharmacogenomics
Chemotherapy Response
Fluorouracil Toxicity. Evidence: 8/10. Source: PMID 19104657. Typical Risk.
Capecitabine Toxicity. Evidence: 8/10. Source: PMID 25782327. Typical Risk.
Drug Metabolism Enzyme Activity
DPD Enzyme Activity. Evidence: 8/10. Source: PMID 19104657. Normal Activity.
Showing effects for C/C genotype
Fluorouracil Toxicity. Evidence: 8/10. Source: PMID 19104657. Increased Risk.
Capecitabine Toxicity. Evidence: 8/10. Source: PMID 25782327. Increased Risk.
DPD Enzyme Activity. Evidence: 8/10. Source: PMID 19104657. Reduced Activity.
Showing effects for T/C genotype
DPD Enzyme Activity. Evidence: 8/10. Source: PMID 19104657. Slightly Reduced.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Standard dihydropyrimidine dehydrogenase enzyme function is expected with this genetic profile [1]. The body is able to break down fluoropyrimidine chemotherapy drugs at a typical rate [1] [2]. Consequently, the risk of developing severe adverse reactions, such as severe diarrhea, mucositis, or hand-foot syndrome, is not elevated compared to the general population [2] [3]. However, standard chemotherapy side effects can still occur due to other genetic or clinical factors [3]. This genotype represents the most common genetic makeup across all global populations [1]. It serves as the baseline reference for drug metabolism studies [2].
Normal metabolism of fluoropyrimidine drugs; Typical risk of chemotherapy side effects.
Sample genotype: CC (Homozygous)
Two copies of the C allele mean both of the DPYD genes carry the p.Met166Val missense variant [1]. This genotype can lead to a more pronounced reduction in dihydropyrimidine dehydrogenase enzyme activity, slowing down the clearance of fluoropyrimidine chemotherapy drugs [1] [2]. As a result, these medications can accumulate in the body, significantly increasing the risk of severe, potentially life-threatening toxicities [2] [3]. Reported adverse effects include severe neutropenia, gastrointestinal toxicity, and hand-foot syndrome [3] [4]. While clinical guidelines continue to evaluate the precise impact of this variant, clinical evidence suggests a strong association with decreased drug tolerance [3]. Discussing these results with a healthcare provider prior to starting fluoropyrimidine-based therapy is highly recommended [2]. This genetic profile is relatively rare but highly relevant for clinical safety [1].
Significantly slower breakdown of fluoropyrimidine drugs; High risk of severe chemotherapy side effects.
Sample genotype: TC (Heterozygous)
A single copy of the C allele results in a missense change (p.Met166Val) in the dihydropyrimidine dehydrogenase enzyme [1]. This alteration can lead to a slower metabolism of fluoropyrimidine chemotherapy drugs, such as 5-fluorouracil and capecitabine [1] [2]. Studies have shown that individuals with this genotype have an increased likelihood of experiencing severe drug toxicities, including neutropenia, mucositis, and hand-foot syndrome [2] [3]. Although some clinical guidelines classify this variant as having normal function, real-world clinical cohorts frequently report a higher incidence of adverse events in carriers [3] [4]. If chemotherapy is required, discussing these genetic findings with an oncologist can help guide personalized monitoring [2]. This variant is particularly common in European and Middle Eastern populations [1]. Knowing this status beforehand allows medical teams to watch closely for early signs of toxicity [3].
Slower breakdown of fluoropyrimidine drugs; Higher risk of severe chemotherapy side effects.
Variants with shared genetic architecture
rs56038477 · DPYD Gene · Chr 1 · Chemotherapy Toxicity Risk
rs75017182 · DPYD Gene · Chr 1 · Chemotherapy Drug Toxicity
rs17376848 · DPYD Gene · Chr 1 · Chemotherapy Toxicity Risk
Content updated August 2026.
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