Influence of ABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: A systematic review and meta-analysis of observational studies

Autores de IIS La Fe

• Juan Eduardo Megías Vericat

  Autor

• Luis Esteban Rojas Orellana

  Autor

• María José Herrero Cervera

  Autor

• Virginia Bosó Ribelles

  Autor

• Pau Montesinos Fernández

  Autor

• Federico Moscardo Garcia

  Autor

• José Luis Poveda Andrés

  Autor

• Miguel Ángel Sanz Alonso

  Autor

• Salvador F Aliño Pellicer

  Autor

Grupos

• Farmacogenética

• Hematología y Hemoterapia

Abstract

The ABCB1 gene encodes for P-glycoprotein (P-gp), an efflux pump for a variety of xenobiotics. The role of ABCB1 polymorphisms in acute myeloid leukemia (AML) outcomes of standard chemotherapy (cytarabine plus anthracyclines) remains controversial. A systematic search was made of studies evaluating the association between ABCB1 polymorphisms 1236C>T, 2677G>T/A and 3435C>T and effectiveness variables. We found seven cohort studies (1241 patients) showing a significantly higher overall survival (OS) among carriers of the variant allele of 1236C>T at year 4 (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.07-2.01), 2677G>T/A at years 4-5 (OR: 1.37, 95% CI: 1.01-1.86) and 3435C>T at years 3 (OR: 1.41, 95% CI: 1.03-1.94) and 4-5 (OR: 1.42, 95% CI: 1.05-1.91). In the subgroup analysis according to ethnicity, Caucasians carrying variant allele showed consistent results in OS. ABCB1 influence upon complete remission could not be demonstrated. Future studies based on larger populations and multiethnic groups should help clarify the effect of P-gp polymorphisms upon other outcomes.

Keywords

• P-GLYCOPROTEIN EXPRESSION; RESISTANCE-RELATED PROTEIN; MESSENGER-RNA EXPRESSION; MDR1 GENE POLYMORPHISM; POOR PROGNOSTIC GROUP; INDEPENDENT PREDICTORS; CLINICAL-SIGNIFICANCE; C3435T POLYMORPHISM; RISK; ASSOCIATION