Association of genetic polymorphisms of CYP2E1 and MPO genes with acute leukemia risk: a meta-analysis

There is a possible association between acute leukemia (AL) and polymorphisms in genes coding for cytochrome P4502E1 (CYP2E1) and myeloperoxidase (MPO), the enzymes both involved in the metabolism and bioactivation of xenobiotic compounds, including benzene especially. Previous studies reported conflicting results. Therefore, a meta-analysis of available molecular epidemiologic studies was performed to comprehensively investigate the association between CYP2E1 RsaI/PstI polymorphism as well as MPO 463G>A genetic variants and AL risk. We systematically searched Pubmed, Web of Science, and Wanfang databases to identify eligible molecular epidemiologic studies up to March 1st, 2016. The effects of each polymorphism were pooled using either fixed or random effect models according to the heterogeneity of the studies. A total of 14 individual case-control studies from 13 articles, concerning polymorphism variants in these two genes (8 studies for CYP2E1 and 6 studies for MPO) with risk to AL were included for analysis, with 2593 cases and 3442 controls involved. Overall, the c2 variant allele of CYP2E1 RsaI/PstI polymorphism may slightly increase AL risk (dominant model: OR=1.46, 95% CI=1.05-2.02, P=0.02; heterozygous model: OR=1.44, 95% CI=1.03-2.00, P=0.03; allelic model: OR=1.42, 95% CI=1.05-1.92, P=0.02) despite a potential publication bias, while MPO 463G>A polymorphism was significantly associated with attenuated risk to AL (dominant model: OR=0.62, 95% CI=0.46-0.84, P=0.002; heterozygous model: OR=0.62, 95% CI=0.51-0.75, P<0.001; allelic model: OR=0.75, 95% CI=0.61-0.93, P=0.007). Subgroup analysis by AL type further showed that there was a significant association between MPO 463G>A polymorphism and decreased risk of acute myeloid leukemia (AML) (OR=0.25, 95% CI=0.15-0.43, P<0.001 for dominant model), rather than acute lymphoblastic leukemia (ALL), which was found associated with CYP2E1 PstI polymorphism (OR=1.45, 95% CI=1.03-2.06, P=0.04 for dominant model). Conclusions: The meta-analysis suggests that CYP2E1 RsaI/PstI polymorphism is associated with elevated AL risk, while MPO 463G>A allele may have a protective function against leukemogenesis.