Tamoxifen P450 2D6 Genotyping

CPT: 81226
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Test Details

Synonyms

  • DME Genotyping

Use

This testing can assist with customizing drug therapy by providing metabolic activity information that may explain patient drug responses relevant to CYP2D6 genetic variability. The cytochrome P450 (CYP450) enzymes metabolize many drugs. Individual genetic differences of cytochrome P450 activity can result in the total absence of metabolism to ultrafast metabolism of certain drugs.

Limitations

This assay does not detect other variants in the CYP2D6 gene that may affect metabolic activity. The metabolism of drugs is also influenced by ethnicity, diet, and other medications. All factors should be considered prior to initiating new therapy. This testing does not rule out the possibility of variant alleles in other drug metabolism pathways.

Methodology

DNA analysis of the Cytochrome P450 2D6 gene (OMIM 124030) is performed using primer extension chemistry. Multiplex PCR amplifies DNA fragments containing the variants below. Primer extension then generates a biotin-labeled product to permit flow-sorted detection of both normal and variant sequences. Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur.

Alleles detected:

*1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *29, *35, *41, and gene duplications.

Variant *5 is a gene deletion. Copy number of duplicated alleles is not determined. Duplications are often functional (whole gene) but may be nonfunctional (partial gene). It is not always possible to determine which allele is duplicated.

*1 represents detection of the normal sequence for the variants tested.

Additional Information

Cytochrome P450 is involved in the metabolism of up to 25% to 30% of all clinically used drugs. Variants in the CYP2D6 gene can result in ultrarapid, normal (extensive), intermediate to normal, intermediate, and poor metabolizer phenotypes. Variants in P450 genes may enhance drug metabolism while others may slow it.

Tamoxifen undergoes significant metabolism to produce several primary and secondary metabolites, including endoxifen. This metabolism appears to be important in the clinical effectiveness of the drug. The CYP2D6 can play an important role in this process. Studies have shown that women who were 2D6 poor or intermediate metabolizers are more likely to have increased breast cancer recurrence and mortality rates when compared to those who were normal metabolizers. Additionally, the co-administration of 2D6 inhibitors, such as paroxetine and fluoxetine, appears to decrease the effectiveness of tamoxifen, even in normal metabolizers, by inhibiting is metabolic activation through 2D6. When considering tamoxifen therapy, it may be useful to consider 2D6 metabolizer status and concomitant use of 2D6 inhibitors.

Specimen Requirements

Specimen

Whole blood or LabCorp buccal swab kit (the buccal swab collection kit contains instructions for the use of a buccal swab, PeopleSoft N° 3177).

Volume

7 mL whole blood or LabCorp buccal swab kit

Minimum Volume

3 mL whole blood or two buccal swabs

Container

Lavender-top (EDTA) tube, yellow-top (ACD) tube, or LabCorp buccal swab kit

Storage Instructions

Maintain specimen at room temperature or refrigerate at 4°C.

Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; wet buccal swab; one buccal swab

Clinical Information

Special Instructions

This test is identical in all operational aspects to 511230; only the report content is different, with wording specific to metabolism and response to the drug, tamoxifen.

References

Dutch Pharmacogenetics Working Group (DPWG) guideline information for tamoxifen and CYP2D6. 2011 www.pharmgkb.org/guideline/PA166104966.
FDA review of tamoxifen metabolism by cytochrome P450 2D6. http://fda.gov/ohrms/dockets/ac/06/briefing/2006-4248B -01-FDA-Tamoxifen%20Background%20Summary%20Final.pdf.
Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015 Aug;98(2):127-134.
Jin Y, Desta Z, Stearns V, et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005 Jan;97(1):30-39.
LabCorp Pharmacogenetic Testing flyer (L14582). Available upon request.
Province MA, Goetz MP, Brauch H, et al. CYP2D6 genotype and adjuvant tamoxifen: Meta-analysis of heterogeneous study populations. Clin Pharmacol Ther. 2014 Feb;95(2):216-227.24060820

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
511280 Tamoxifen 2D6 Genotyping 504202 2D6 Genotype: 40425-1
511280 Tamoxifen 2D6 Genotyping 504203 2D6 Metabolic Activity: 79715-9
511280 Tamoxifen 2D6 Genotyping 504401 Interpretation: 72880-8
511280 Tamoxifen 2D6 Genotyping 504402 CYP2D6 Information: 49549-9
511280 Tamoxifen 2D6 Genotyping 504403 Tamoxifen 2D6 Genotyping N/A

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