CYP1A1 and CYP2D6 Polymorphisms and Susceptibility to Chronic Myelocytic Leukaemia.

Abstract

CYP1A1 and CYP2D6 are both xenobiotic metabolizing enzymes belonging to the CYP450 enzyme family. Polymorphisms in these genes vary between individuals, resulting in dissimilar patterns of susceptibility to the effects of carcinogenic substances and drugs. In a prospective study, the influence of CYP1A1*2C and CYP2D6*4 gene polymorphisms on the susceptibility to chronic myelocytic leukaemia (CML) were investigated. Prevalence of CYP1A1*2C and CYP2D6*4 was detected in blood specimens from three hundred participants - two hundred patients and a hundred healthy individuals as a control group, using PCR-RFLP. CYP1A1 Ile/Val and Val/Val genotype frequency in our study population was 82% & 15% in CML patients and 55% & 8% in controls, respectively. This suggests that carriers had an elevated risk (OR=18.38, 95% CI=7.364-45.913, p value; =0.000 and OR=23.125,95 % CI=7.228-73.980, p value=0.000, respectively). Individuals carrying the CYP2D6 heterozygous genotype (IM) were notably fewer in number within the CML group at 43.5%, as opposed to 93% of the controls. This suggests that the IM genotype may have a prophylactic function in lowering CML risk (OR=0.036, 95% CI=0.005-0.271, p value =0.001). In spite of the distribution of the homozygous mutant (PM) genotype being higher in cases with CML (87% as opposed to 6% in the control), this difference was deemed non-significant (OR=0.558, 95% CI=0.064-4.845, p value =0.597). These findings indicate that polymorphic CYP1A1 and CYP2D6 genes affect the susceptibility to CML.