Novel Insights Into Etiologies of Leukemia: A HuGE Review and Meta-Analysis of CYP1A1 Polymorphisms and Leukemia Risk

We conducted a meta-analysis to investigate the association of 2 single nucleotide polymorphisms in the cytochrome P450, family 1, subfamily 1A1 gene (CYP1A1), CYP1A1*2A and CYP1A1*2C, with the risk of developing different subtypes of leukemia in adults and children. A total of 26 studies published between 1999 and 2011 were identified by searching the PubMed, EMBASE, Medline, and Web of Science databases. The odds ratios for the CYP1A1 polymorphisms and leukemia risk were calculated. The cumulative evidence in genetic associations was graded by using the Venice criteria of the Human Genome Epidemiology Network (Atlanta, Georgia). The results showed that the cumulative evidence was moderate for the association of the CYP1A1*2A variant with leukemia in Caucasians and with childhood acute lymphoid leukemia in Caucasians. In addition, there was moderate evidence that children who carry both the CYP1A1*2A variant and the glutathione S-transferase M1 null genotype have an increased risk of acute lymphoid leukemia. For the CYP1A1*2C polymorphism, the cumulative evidence of an association with leukemia risk was moderate for adults and weak for children. Logistic regression analysis demonstrated an interaction between the CYP1A1*2C polymorphism and age. This meta-analysis showed that the CYP1A1*2A and CYP1A1*2C polymorphisms were associated with an increased risk of leukemia, and that the associations might vary by ethnicity, gene-gene interactions, age, and leukemia subtype.