Clinical significance of ABCB1 genotyping in oncology.
BACKGROUND
P-glycoprotein (Pgp) is a drug efflux pump that transports natural products, including taxanes and other chemotherapeutic agents, from cells. Several frequent polymorphisms in ATP binding cassette gene B1 (ABCB1) may influence Pgp levels and drug efflux. The purpose of this review was to assess the clinical significance of ABCB1 polymorphisms in oncology.


METHODS
Peer-reviewed studies were identified through a search of PubMed/MEDLINE (1990-2008) and the ASCO abstracts (2003-2008) database. Included studies described clinical trials where ABCB1 genotyping was performed in patients with cancer. Search terms included ABCB1, Pgp, docetaxel, paclitaxel, irinotecan, imatinib, and anticancer agent. Studies were excluded if the manuscript was not available in English.


RESULTS
The influence of polymorphisms in ABCB1 2677G>T/A, 3435C>T, and 1236C>T and progression-free and overall survival in 309 patients from the Australian Ovarian Cancer Study treated with paclitaxel/carboplatin demonstrated that compared to homozygote GG carriers at 2677, women with the minor T/A alleles were significantly less likely to relapse following treatment. Other trials of ABCB1 genotyping in breast and prostate cancer patients receiving taxanes have shown inconsistent results. Pharmacokinetic studies where ABCB1 was genotyped and patients received irinotecan or imatinib have also shown inconsistent results.


CONCLUSIONS
A number of commercially available drugs are substrates for Pgp, and the ABCB1-variant genotypes are frequent and functionally significant, which may have future implications for drug dosing.
Hamidovic
Alma
A
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792, USA.
Hahn
Kristine
K
Kolesar
Jill
J
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000502:physiology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods; D016896:Treatment Outcome
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents