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

• Published in: The pharmacogenomics journal 2015-04, Vol.15 (2), p.109-118
• Main Authors: Megías-Vericat, J E, Rojas, L, Herrero, M J, Bosó, V, Montesinos, P, Moscardó, F, Poveda, J L, Sanz, M Á, Aliño, S F
• Format: Article
• Language: English
• Subjects: 45/23; 45/77; 692/699/1541; Acute myeloid leukemia; Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Anthracycline; Anthracyclines - therapeutic use; ATP Binding Cassette Transporter, Sub-Family B - genetics; Biomedical and Life Sciences; Biomedicine; Chemotherapy; Child; Child, Preschool; Cohort Studies; Cytarabine; Cytarabine - therapeutic use; Drug metabolism; Female; Gene Expression; Genetic aspects; Genetic polymorphisms; Health aspects; Human Genetics; Humans; Infant; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Male; Meta-analysis; Middle Aged; Minority & ethnic groups; Myeloid leukemia; Observational studies; Observational Studies as Topic; Oncology; P-Glycoprotein; Pharmacotherapy; Polymorphism, Genetic - genetics; Population studies; Psychopharmacology; Remission; review; Treatment Outcome; Xenobiotics; Young Adult
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2014.80

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.