Gene variants of CYP1A1 and CYP2D6 and the risk of childhood acute lymphoblastic leukaemia; outcome of a case control study from Kashmir, India

Studies on associations of various polymorphisms in xenobiotic metabolizing genes with different cancers including acute lymphoblastic leukaemia (ALL) are mixed and inconclusive. The current study analyzed the relationship between polymorphisms of phase I xenobiotic metabolizing enzymes, cytochromes P450 1A1 (CYP1A1) and CYP2D6 and childhood ALL in Kashmir, India. We recruited 200 confirmed ALL cases, and an equal number of controls, matched for sex, age and district of residence to the respective case. Information was obtained on various lifestyle and environmental factors in face to face interviews with the parents/attendants of each subject. Genotypes of CYP1A1 and CYP2D6 were analyzed by polymerase chain reaction and restriction fragment length polymorphism method. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Compared to the GG genotype, we found a higher ALL risk in subjects who harbored variant (AA) genotype (OR=20.9; 95% CI: 6.01-73.1, P<0.0001) and AG genotype (OR=42.6; 95% CI: 8.3-217.5, P<0.0001) of CYP2D6*4 polymorphism. Although, we found a significant association of CYP1A1*2A polymorphism with ALL risk, but the risk did not persist in the adjusted model (OR=6.76; 95% CI: 0.63-71.8, P=0.100). The study indicates that unlike CYP1A1*2A, CYP2D6*4 polymorphism is associated with ALL risk. However, more replicative studies with larger sample size are needed to substantiate our findings.