Poor metabolizers at the cytochrome P450 2D6 and 2C19 loci are at increased risk of developing adult acute leukaemia

We have genotyped over 550 cases of acute leukaemia and 950 matched control s from a population-based case-control study, to investigate the impact cyt ochrome P450s 2D6, 2C19 and 1A1 have on susceptibility to adult acute leuka emia. Analysis included potential associations between polymorphic status a nd acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), plus the FAB and cytogenetic subtypes therein, A significant increased risk was found for CYP2D6 poor metabolizer phenotype and acute leukaemia [odds rati o (OR)= 1.69, 95% confidence interval (CI) 1.17-2.43], a risk also found in AML and ALL. No interaction was found with smoking, However, a significant age-related association between CYP2D6 polymorphism and acute myeloid leuk aemia implied that the excess risk was confined to persons aged 40 years an d over (OR 2.38, 95% CI 1.53-3.71). Amongst AML cases, increased odds ratio s were observed in both ne-novo (OR 1.54, 95% CI 1.02-2.32) and secondary l eukaemia (OR 2.83, 95% CI 0.91-8.77), and among patients with a chromosomal abnormality (OR 2.00, 95% CI 1.11-3.61), An increased risk was found for t he CYP2C19 poor metabolizer phenotype (OR 1.68, 95% CI 0.97-2.92) which was also present in AML and ALL. For this CYP450 locus, an increased risk was suggested in secondary leukaemia (OR 2.67, 95% CI 0.44-16.3) and amongst AM L cases with a chromosomal abnormality (OR 6.72, 95% CI 2.22-20.4). No diff erence in CYP1A1 genotype distribution was found for acute leukaemia, AML, ALL or any other diagnostic classification group used. No significant inter actions between CYP2D6, CYP2C19 or CYP1A1 were found. Pharmacogenetics 10:6 05-615 (C) 2000 Lippincott Williams & Wilkins.