What you carry at this position in your DNA and what research says about it.
Chemotherapy Toxicity Risk: 8/10 evidence, 9 publications.
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Sample genotype (not yours): T/T
Typical Chemotherapy Toxicity Risk
Normal dihydropyrimidine dehydrogenase enzyme activity is expected with this genotype. This means there is a standard risk of side effects if treated with common fluoropyrimidine chemotherapy drugs.
What this genotype means: Normal dihydropyrimidine dehydrogenase enzyme activity; Typical risk of fluoropyrimidine chemotherapy side effects; Standard dosing of fluorouracil or capecitabine is typically appropriate.
Sample genotype (not yours): A/A
Severe Chemotherapy Toxicity Risk
Profound deficiency in dihydropyrimidine dehydrogenase enzyme activity is caused by having two copies of the variant allele. This leads to an extremely high risk of life-threatening toxicity if exposed to standard doses of certain chemotherapy drugs.
What this genotype means: Severe or complete dihydropyrimidine dehydrogenase deficiency; Extremely high risk of life-threatening chemotherapy toxicity; CPIC: poor metabolizer, fluoropyrimidines flagged high-toxicity.
Sample genotype (not yours): T/A
Increased Chemotherapy Toxicity Risk
Decreased dihydropyrimidine dehydrogenase enzyme activity occurs with one copy of the variant allele. This significantly increases the risk of severe, potentially life-threatening toxicities if treated with standard doses of certain chemotherapy drugs.
Gene function and biological role
Gene Function: The DPYD gene encodes dihydropyrimidine dehydrogenase, a critical enzyme responsible for breaking down uracil and thymine [1]. This enzyme is also the primary pathway for metabolizing fluoropyrimidines, a class of chemotherapy drugs widely used to treat solid tumors such as colorectal, breast, and stomach cancers [2]. When enzyme activity is reduced, these drugs can build up to toxic levels in the body, leading to severe and potentially life-threatening side effects [1] [2].
Variant Impact: A single nucleotide change in the DPYD gene, rs67376798 (also known as c.2846A>T or p.Asp949Val), causes an amino acid substitution from aspartate to valine in the dihydropyrimidine dehydrogenase enzyme [3]. This molecular change significantly reduces the enzyme's catalytic activity, leaving only about 35 percent of normal function [4]. As a result, individuals carrying this variant have a significantly decreased ability to clear fluoropyrimidine chemotherapy drugs like fluorouracil and capecitabine from their systems [4] [5]. This leads to a dramatically increased risk of severe, early-onset drug toxicities, including severe diarrhea, neutropenia, and hand-foot syndrome [5].
Key Insight: Even a single copy of this variant can reduce dihydropyrimidine dehydrogenase enzyme activity to about 35 percent of normal, making standard doses of common cancer drugs highly toxic.
Location: DPYD. Chromosome 1 · 1p21.3 · 97.1 Mb
Estimated prevalence by population
Global 99.3%; European 98.8%; African 99.8%; East Asian 100.0%; South Asian 99.9%; Americas 99.7%; Ashkenazi 99.9%; Middle Eastern 100.0%; Amish 100.0%.
Estimated TT genotype frequency.
Global 0.7%; European 1.2%; African 0.2%; East Asian 0.0%; South Asian 0.1%; Americas 0.3%; Ashkenazi 0.1%; Middle Eastern 0.0%; Amish 0.0%.
Estimated TA genotype frequency.
Global < 0.1%; European < 0.1%; African < 0.1%; East Asian 0.0%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi < 0.1%; Middle Eastern 0.0%; Amish 0.0%.
Estimated AA genotype frequency.
Showing effects for T/T genotype
Pharmacogenomics
Chemotherapy Response
Fluorouracil Toxicity. Evidence: 8/10. Source: PMID 29152729. Typical Risk.
Capecitabine Toxicity. Evidence: 8/10. Source: PMID 29152729. Typical Risk.
Tegafur Toxicity. Evidence: 8/10. Source: PMID 23930673. Typical Risk.
Hand-Foot Syndrome. Evidence: 5/10. Source: PMID 27995989. Typical Risk.
Showing effects for A/A genotype
Fluorouracil Toxicity. Evidence: 8/10. Source: PMID 29152729. Severe Risk.
Capecitabine Toxicity. Evidence: 8/10. Source: PMID 29152729. Severe Risk.
Tegafur Toxicity. Evidence: 8/10. Source: PMID 23930673. Severe Risk.
Hand-Foot Syndrome. Evidence: 5/10. Source: PMID 27995989. Severe Risk.
Showing effects for T/A genotype
Fluorouracil Toxicity. Evidence: 8/10. Source: PMID 29152729. Increased Risk.
Capecitabine Toxicity. Evidence: 8/10. Source: PMID 29152729. Increased Risk.
Tegafur Toxicity. Evidence: 8/10. Source: PMID 23930673. Increased Risk.
Hand-Foot Syndrome. Evidence: 5/10. Source: PMID 27995989. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Two copies of the reference T allele mean your dihydropyrimidine dehydrogenase (DPD) enzyme functions at a normal level [1]. This enzyme is responsible for breaking down fluoropyrimidine chemotherapy drugs like fluorouracil and capecitabine [1] [2]. Because your enzyme activity is typical, you do not have the elevated risk of severe, early-onset toxicities associated with DPYD deficiency [2]. Other genetic or clinical factors can still influence drug response [2]. Your risk of severe side effects like severe diarrhea, neutropenia, or hand-foot syndrome remains at the baseline level [2] [3].
Normal dihydropyrimidine dehydrogenase enzyme activity; Typical risk of fluoropyrimidine chemotherapy side effects; Standard dosing of fluorouracil or capecitabine is typically appropriate.
Sample genotype: AA (Homozygous)
Two copies of the variant A allele lead to a severe or complete deficiency in dihydropyrimidine dehydrogenase (DPD) enzyme activity [1]. Without functioning DPD, your body cannot effectively metabolize fluoropyrimidine chemotherapy drugs like fluorouracil, capecitabine, or tegafur [1] [2]. Exposure to standard doses of these medications can result in extreme, life-threatening toxicities, including severe bone marrow suppression, mucosal inflammation, and organ damage [2] [3].
Severe or complete dihydropyrimidine dehydrogenase deficiency; Extremely high risk of life-threatening chemotherapy toxicity; CPIC: poor metabolizer, fluoropyrimidines flagged high-toxicity.
Sample genotype: TA (Heterozygous)
One copy of the variant A allele results in a dihydropyrimidine dehydrogenase (DPD) enzyme with decreased function [1]. This reduced activity impairs your body's ability to break down and clear fluoropyrimidine chemotherapy drugs, such as fluorouracil, capecitabine, and tegafur [1] [2]. Consequently, standard doses of these medications can lead to a rapid buildup of toxic drug levels [2]. This significantly increases your risk of experiencing severe, early-onset adverse reactions, including profound neutropenia, severe diarrhea, and hand-foot syndrome [2] [3]. The CPIC DPYD guideline classifies this as a decreased-function genotype [2].
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
Phenotypic and clinical implications of variants in the dihydropyrimidine dehydrogenase gene.
Content updated August 2026.
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