Fluoropyrimidines and DPYD

We offer two pharmacogenomic tests to identify genetic variants associated with the metabolism of chemotherapy drugs in the fluoropyrimidine drug class, such as 5-fluorouracil and capecitabine. This testing specifically targets the DPYD gene, which plays a crucial role in the breakdown of these medications in the body. By analyzing specific variants within the DPYD gene, physicians and other healthcare professionals can assess a patient's risk of adverse reactions to these chemotherapy drugs, including severe fluoropyrimidine-induced toxicity and potentially life-threatening outcomes. In addition, pathogenic homozygous or compound heterozygous variants within DPYD are associated with dihydropyrimidine dehydrogenase (DPD) deficiency, a rare condition in which patients may experience no symptoms at all or something as severe as a convulsive disorder with motor and intellectual disabilities.

Genotype testing (Mayo ID: DPYDQ) is used for the assessment of common variants associated with DPYD deficiency. Full sequencing (Mayo ID: DPYDZ) is used based on patient or physician preference or when there is suspicion of rare or novel variants. Full sequencing also can be used when the patient's phenotype does not align with expected genotype results or for patients from ancestral populations that have not been genetically well-characterized.

Key testing

• DPYDQ | Dihydropyrimidine Dehydrogenase Genotype, Varies
  • Identifies individuals with common genetic variants in DPYD to anticipate increased risk of toxicity when prescribed 5-fluorouracil or capecitabine chemotherapy treatment.
• DPYDZ | Dihydropyrimidine Dehydrogenase, DPYD Full Gene Sequencing, Varies
  • Identifies individuals with any genetic variant in DPYD to anticipate increased risk of toxicity when considering 5-fluorouracil and capecitabine chemotherapy treatment.
  • Finds common and rare variants not included in the targeted genotyping assay associated with decreased or absent dihydropyrimidine dehydrogenase (DPD) enzyme activity in individuals with suspected DPD deficiency.

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Irinotecan and UGT1A1

UGT1A1 plays a critical role in metabolizing irinotecan, a chemotherapy used to treat solid tumors such as colon, rectal, and lung cancers. Patients with reduced or deficient UGT1A1 activity are at increased risk of toxicity. Lower activity impairs the metabolism of irinotecan's active metabolite, SN-38, leading to high SN-38 levels and potentially severe side effects.

The increased SN-38 concentration is associated with a heightened risk of severe neutropenia, which can be life-threatening when combined with diarrhea. Irinotecan’s drug label recommends monitoring individuals with TA repeat variants (either homozygous or heterozygous), particularly those receiving the drug every three weeks, due to their higher risk of severe neutropenia. UGT1A1 testing identifies patients at elevated risk for irinotecan toxicity, supporting safer, more personalized dosing.

Key testing

• U1A1Q | UDP-Glucuronosyltransferase 1A1 TA Repeat Genotype, UGT1A1, Varies
  • Identifies individuals with common genetic UGT1A1TA5 (*36), TA7 (*28), and *6 variants to predict increased risk of irinotecan-induced toxicity and other drugs metabolized by UGT1A1.
• UGTFZ | UDP-Glucuronosyltransferase 1A1 (UGT1A1), Full Gene Sequencing, Varies
  • Identifies individuals who are at increased risk of adverse drug reactions or hyperbilirubinemia when taking drugs that are metabolized by UGT1A1, including atazanavir, belinostat, irinotecan, nilotinib, pazopanib, and sacituzumab govitecan.
  • Follow-up testing for individuals with a suspected UGT1A1 variant who had negative TA repeat region testing.
  • Establishes carrier status or a diagnosis of either Crigler-Najjar syndrome or Gilbert syndrome.

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Tamoxifen and CYP2D6

The CYP2D6 gene is highly variable with over 100 named alleles. The gene may be deleted, duplicated, and multiplied, and can have multiple sequence variations. In addition, some individuals have genes that are hybrids of CYP2D6 and the CYP2D7 pseudogene.

Some individuals have CYP2D6 variants that result in the synthesis of an enzyme with decreased or absent catalytic activity. These individuals may process CYP2D6-metabolized medications more slowly. CYP2D6 duplications and multiplications involving active alleles may result in the ultrarapid metabolism of CYP2D6-metabolized drugs. CYP2D6 genotype results are used to predict metabolizer phenotypes.

Key testing

• 2D6Q | Cytochrome P450 2D6 Comprehensive Cascade, Varies
  • Provides information relevant to tamoxifen, codeine, and tramadol, as well as other medications metabolized by cytochrome P450 2D6.
  • Determines the exact genotype when other methods fail to generate this information or if genotype-phenotype discord is encountered clinically.
  • Identifies precise genotype when required (e.g., drug trials, research protocols).
  • Identifies novel variants that may interfere with drug metabolism (when reflex to sequencing is performed).

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Therapeutic drug monitoring

Key testing

• BUAUC | Busulfan, Intravenous Dose, Area Under the Curve, Plasma
  • Guides dosage adjustments to achieve complete bone marrow ablation while minimizing dose-dependent toxicity.
• MITAN | Mitotane, Plasma
  • Verifies that therapeutic concentrations (14–20 mcg/mL) are maintained to optimize treatment for adrenal cortical carcinoma.
• MTHX | Methotrexate, Serum
  • Determines whether methotrexate is being cleared appropriately and verifies that a nontoxic concentration has been attained following therapy.