The influence of genetic factors on the development of different clinical manifestations of toxicity in patients with non-Hodgkin lymphomas
The influence of CYP2D6*4 (G1934A) and CYP2C19*2 (G681A) genes polymorphism on the risk of different toxicity in patients with non-Hodgkin lymphomas were determined to assess their long-term use as a prognostic marker. The association of the inheritance dominant model in CYP2D6*4 gene with an increased risk of toxic effects during courses of chemotherapy was found in investigated patients. The risk of toxic effects increased 5 times in patients with 1934GA and 1934AA genotypes of CYP2D6*4 gene are almost, and 1934GG genotype for that gene reduced the risk of toxic effects. Unfavourable polymorphic variants of CYP2D6*4 gene have been associated with a 5-fold increased risk of haematological toxicity and widespread genomic polymorphic variant of this gene 1934GG reduced the risk of toxic effects. The combination of 1934GG+681GG genotypes in the CYP2D6*4 and CYP2C19*2 genes significantly reduced the risk of hematological toxicities have surveyed patients, and the combination of 1934GA+681GG genotypes on these genes increased the risk almost 9 times. Analysis of the CYP2D6*4 gene polymorphism can be recommended in clinical practice for predicting hematological toxicity. Further studies of toxic effects risk, taking into account concomitant therapy, modifications which may also influence on the toxic effects risk due to regulatory actions on cytochrome oxidase genes, are necessary.