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Pharmacogenetics in Oncology

Pharmacogenetic Markers in Oncology

Pharmacogenomics can play an important role in identifying responders and non-responders to medications, avoiding adverse events and optimising drug dose. Drug labelling may contain information on genomic biomarkers and can describe:

Drug exposure and clinical response variability Mechanisms of drug action
Risk for adverse events Polymorphic drug target and disposition genes
Genotype-specific dosing Trial design features

In addition to RAS, BRAF, EGFR, ERBB2 (HER2), PK3CA, KIT mutation and PD-1, ROS, ALK, and BCR-ABL fusion genes, other genetic pharmacogenetic biomarkers play a role in patients’ responses to oncology therapy.

Pharmacogenomics, an important part of precision medicine, is the study of how a person’s genetic makeup can affect their response to a drug. Healthcare providers can use pharmacogenomic information to help decide the most appropriate treatment for each individual.

The cytochrome P450 (CYP450), a family of enzymes, catalyses the metabolism of many drugs and xenobiotics. The genes that code for these enzymes are polymorphic, which can significantly affect drug metabolism in certain individuals. CYP2D6, CYP2C19 and CYP2C9 are responsible for the metabolism of a large number of commonly prescribed drugs, including warfarin, analgesics, clopidogrel, codeine, tamoxifen, some antidepressants, statins, proton pump inhibitors (PPI) and anti-emetics.

More than 70 allelic variants have been described for the gene that codes CYP2D6. These variants result in four distinct phenotypes: poor metabolisers, intermediate metabolisers, extensive metabolisers and ultrarapid metabolisers. Both the CYP2C9 and the CYP2C19 genes have two major variant alleles that result in enzyme deficiency.

Differences in drug metabolism due to CYP450 gene variants influence plasma levels of both the active drug and its metabolites. Poor metabolisers treated with drugs that are metabolised by these enzymes are at increased risk for prolonged therapeutic effect or toxicity, while ultrarapid metabolisers may not achieve therapeutic plasma levels.

Thiopurine methyltransferase (TPMT) is the primary enzyme responsible for thiopurine drugs (azathioprine, 6-mercaptopurine and 6-thioguanine) metabolism. These drugs are converted in the body to thioguanine nucleotides (TGNs).

Thiopurine therapy targets the replicating cells without overly harming normal cells. TPMT activity is significantly affected by polymorphisms found in the TPMT gene and can lead to different responses to thiopurine therapy.

DPYD gene
DPD stands for dihydropyrimidine dehydrogenase, an enzyme made by the liver that breaks down uracil and thymine. The molecules created when pyrimidines are broken down (5,6-dihydrouracil and 5,6-dihydrothymine) are excreted by the body or used in other cellular processes.

More than 50 mutations in the DPYD gene have been identified in people with dihydropyrimidine dehydrogenase deficiency. DPYD gene mutations interfere with the breakdown of uracil and thymine and result in excess quantities of these molecules in the blood, urine, and the fluid that surrounds the brain and spinal cord (cerebrospinal fluid).

Mutations in the DPYD gene also interfere with the breakdown of drugs with structures similar to the pyrimidines, such as the cancer drugs 5-fluorouracil and capecitabine (two common chemotherapy drugs used as a treatment for a number of different cancers). As a result, these drugs accumulate in the body and cause the severe reactions and neurological manifestations as a result of DPD deficiency.


Pharmacogenetic Testing at Australian Clinical Labs

Our comprehensive Pharmacogenetic tests can detect polymorphisms in genes coding for drug-metabolising enzymes that predispose individuals to metabolising drugs inadequately.

Genes Offered:

Cytochrome P450 including:

List of Oncology Related Genotypes:

GENE Oncology Drug Medicare Rebate
CYP2D6 Tamoxifen
Oxycodone (lesser extent)
CYP2C9 Tacrolimus
CYP2C19 Clopidogrel N/A
CYP2C9/VKORC1 Warfarin N/A
CYP3A5 Tacrolimus N/A
DPYD Fluorouracil
UGT1A1 Belinostat
Thiopurine Methyltransferase (TPMT) Mercaptopurine,
Azathioprine and


When to order:

Before therapy, with adverse reaction or resistance.

How to order:

Fill out our routine Clinical Labs testing request form, list the gene required or group of genes.
Please note that the panel Cytochrome P450 Genes can be ordered separately or together (CYP2D6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, CYP1A2, SLCO1B1 and VKORC1).

Turnaround time:

Results will be available after 7-10 business days from the sample receipt date.

Specimen required:

2x EDTA blood samples.

Test cost:

Cytochrome P450 Comprehensive Gene Panel (including CYP2D6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, CYP1A2, SLCO1B1 and VKORC1): No Medicare rebate available. An out-of-pocket fee of $190 applies.
Note: If any of the genes from the Cytochrome P450 Comprehensive Gene Panel are ordered individually, an out-of-pocket fee of $140 applies, for each gene ordered.
TPMT: Medicare rebate available.
DPYD: No Medicare rebate available. An out-of-pocket fee of $140 applies.
UGT1A1: No Medicare rebate available. An out-of-pocket fee of $195 for UG1 test and $95 for GIL test applies.
Analgesic Dosing (CYP2D6)
: No Medicare rebate available. An out-of-pocket fee of $140 applies.
Clopidogrel Predictor (CYP2C19): No Medicare rebate available. An out-of-pocket fee of $140 applies.
Tamoxifen Predictor (CYP2D6): No Medicare rebate available. An out-of-pocket fee of $140 applies.
Warfarin Predictor (CYP2C9/VKORC1): No Medicare rebate available. An out-of-pocket fee of $150 applies.
Variconazole (CYP2C19): No Medicare rebate available. An out-of-pocket fee of $140 applies.
Proton Pump Inhibitors (CYP2C19): No Medicare rebate available. An out-of-pocket fee of $140 applies.

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The content on our Molecular Cancer Services page is written by National Clinical Director of Molecular Genetic Pathology at Australian Clinical Labs, Associate Professor Mirette Saad


Assoc. Prof. Mirette Saad

Lab: Clayton
Speciality: Chemical Pathology and Molecular Genetics
Areas Of Interest: Cancer Genetics, Antenatal Screening, NIPT, Endocrine, Fertility Testing and Research, Medical Teaching
Phone: 1300 134 111
Email: mirette.saad@clinicallabs.com.au

Associate Professor Mirette Saad is a Consultant Chemical Pathologist and the National Director of Molecular Genetics at Australian Clinical Labs. She has a Fellowship with honours in Chemical and Molecular Pathology, with Microbiology sub-speciality, from Suez Canal University, Egypt. A/P Saad received her NHMRC sponsored PhD degree in Cancer Genetics from Melbourne University and Peter MacCallum Cancer Institute. Along with her teaching and research roles, A/P Saad is a registered medical practitioner with AHPRA, a Chemical Pathology Fellow (FRCPA) at the Royal College of Pathologists of Australasia and a Member of the Australasian Association of Clinical Biochemists (MAACB). She is a Chair of the RCPA Chemical Pathology Advisory Committee, Member of the RCPA Genetic Advisory Committee, AACB and a Chair of the Precision Medicine Services at Australian Clinical Labs. At Clinical Labs, A/Prof Mirette Saad leads the Molecular Genetic testing for non-invasive prenatal testing (NIPT), antenatal screening, personalised drug therapy and cancer.

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