Response to the same drug administered at the same dosage may vary greatly among individuals.
This is partly related to individual differences in the absorption, metabolism and elimination of drugs. In other instances the differences involve the specific drug action: e.g., distinctive individual differences may exist in the drug link to its target.
These differences are based on the action of a great number of enzymes, each of which is produced by a specific gene. Many of these genes are polymorphic in the population and these genetic variants produce enzymes with varying levels of metabolic activity or enzymes whose activity affects the efficacy and/or toxicity of a specific drug.
Chemotherapy is of critical importance in cancer treatment but it may cause important adverse side-effects which may vary greatly among individuals and among drug combinations.
Chemotherapeutic agents are almost invariably toxic towards normal cells as well as cancer cells. Recent advances in analytical methods and genome sequencing have led to identify allele variants of genes involved in drug metabolism, pharmacokinetics and pharmacodynamics; these changes may be related to drug chemo-sensitivity or tolerance.
This kit detects and identifies 126 polymorphisms in 58 genes involved in the absorption, distribution, metabolism, excretion and toxicity of chemotherapy agents by MALDI-TOF mass spectrometry combined with Single Base Extension technology.
Among others, the following genes are analyzed: DPYD, UGT1A1, CYP2D6, CYP3A4, CYP3A5, CYP2C9, ABCB1, GSTP1, TSER, ERCC1, RRM1, XRCC1, CDA.
Fluoropyrimidines may be associated with gastrointestinal and hematological toxicity which can be very severe if a dihydropyrimidine dehydrogenase (DPD) deficiency occurs, as this enzyme performs a key role in the breakdown of these drugs. In fact, polymorphism of the gene that codes for DPD enzyme, DPYD, may result in a reduced enzymatic activity.
Irinotecan may be associated with severe gastrointestinal and hematological toxicity resulting from a deficit concerning glucuronic acid conjugation metabolism related to the UGT1A enzyme, especially if a mutation occurs in the promoter region of the gene (wild-type allele *1 [(TA)6TAA] and mutant *28 [(TA)7TAA]).
As AIOM guidelines suggest, pharmacogenetic testing for these genes is recommended:
The response to Tamoxifen varies widely among women. This may be at least partly caused by the highly polymorphic nature of the CYP2D6 gene. In women who have non-functional allelic variants such as *3, *4, *5, e *6 Tamoxifen is less active and probability of cancer recurrence is thus increased. Genetic testing helps the oncologist to preliminary assess whether a patient may benefit from Tamoxifen and avoid the concurrent use of GYP2D6 inhibitors which affect Tamoxifen metabolism and conversion into its active metabolites.
The analysis of GSTP1 gene polymorphism with reference to the 1578A>G variant can be of great clinical importance to identify and select patients who are more likely to benefit from a platinum based chemotherapy.
Peripheral blood in 2 6ml EDTA test tubes.
The test is performed by Mass Array Analyzer within 7 working days from sample receipt.