Combined GSTTI Null, GSTM! Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukaemia

Purpose: Glutathione-S-transferase (GSTTI and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTTI, GSTMI and XPD polymorphisms in newly diagnosed chronic myeloid leukaemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML. Patients and Methods: This case-control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTTI null and GSTMI null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers. Results: GSTTI and GSTMI null polymorphisms were detected in 42.7% and 61.3% of cases, respectively compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes is cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20% and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTTI/GSTMI null with XPD Lys/Lys, and GSTMI null with XPD Lys/Lys. Conclusions: In conclusion, GSTTI null, GSTMI null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with studied polymorphisms, while CML phases were associated with GSTTI null polymorphisml