Association between CYP1A1 Ile462Val variation and acute leukemia risk: meta-analyses including 2164 cases and 4160 controls

PLoS One. 2012;7(10):e46974. doi: 10.1371/journal.pone.0046974. Epub 2012 Oct 4.

Abstract

Background: Previously, CYP1A1 Ile462Val polymorphism has been indicated to be a risk factor for several malignancies. Increasing reports have focused on the association of CYP1A1 Ile462Val polymorphisms with susceptibility to acute leukemia and have generated controversial results. The goal of the present study was to derive a more precise estimation of the relationship.

Methods: Relevant literature has been rigorously searched and screened. Eligible studies were identified for the period up to Apr 2012. Meta-analyses evaluating the association of CYP1A1 Ile462Val variation with acute leukemia were carried out. Subgroup analyses on ethnicity, clinical types and source of controls were further performed.

Results: A total of thirteen publications including fourteen case-control studies with 2164 cases and 4160 controls were selected for analysis. The overall data indicated a significant association of CYP1A1 Ile462Val polymorphism with acute leukemia risk (Val/Val vs Ile/Ile OR = 1.49; 95% CI = 1.11-1.98; dominant model: OR = 1.26; 95% CI = 1.05-1.51; recessive model: OR = 1.38; 95% CI = 1.04-1.83). In subgroup analysis on ethnicity, increased risk was shown among mixed ethnicities (Val/Val vs Ile/Ile: OR = 2.36; 95% CI = 1.46-3.82; dominant model: OR = 1.37; 95% CI = 1.01-1.86; recessive model: OR = 2.20; 95% CI = 1.37-3.53) but not Asians or Caucasians. In subgroup analysis on clinical types, increased risk was observed in the acute lymphocytic leukemia (ALL) subgroup (Val/Val vs Ile/Ile: OR = 2.06; 95% CI = 1.42-3.01; recessive model: OR = 1.91; 95% CI = 1.32-2.76) but not in the acute myeloid leukemia (AML) subgroup.

Conclusion: The results of the present study suggest that CYP1A1 Ile462Val polymorphism might be a low-penetrant risk factor for acute leukemia. Subgroup analyses suggest that homozygous Val/Val alleles might modify the susceptibility to ALL.

Publication types

  • Meta-Analysis

MeSH terms

  • Acute Disease
  • Case-Control Studies
  • Cytochrome P-450 CYP1A1 / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Leukemia / enzymology*
  • Leukemia / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • Cytochrome P-450 CYP1A1

Grants and funding

The authors have no support or funding to report.