1. ¹Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
2. ²Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
3. ³Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany
4. ⁴Tumor Biology Center at the Albert-Ludwigs-University, Freiburg, Germany
5. ⁵Department of Medical Oncology, Erasmus MC – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Correspondence: A Sparreboom, (alex.sparreboom@stjude.org)

Received 24 August 2006; Accepted 20 September 2006.

Abstract

To explore retrospectively the relationships between paclitaxel pharmacokinetics and three known, non-synonymous single-nucleotide polymorphisms (SNPs) in SLCO1B3, the gene encoding organic anion transporting polypeptide (OATP)1B3. Accumulation of [³H]paclitaxel was studied in Xenopus laevis oocytes injected with cRNA of Oatp1b2, OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and NTCP. The 334T>G (Ser112Ala), 699G>A (Met233Ile), and 1564G>T (Gly522Cys) loci of SLCO1B3 were screened in 475 individuals from five ethnic groups and 90 European Caucasian cancer patients treated with paclitaxel. Only OATP1B3 was capable of transporting paclitaxel to a significant extent (P=0.003). The 334T>G and 699G>A SNPs were less common in the African-American and Ghanaian populations (P<0.000001). Paclitaxel pharmacokinetics were not associated with the studied SNPs or haplotypes (P>0.3). The studied SNPs in SLCO1B3 appear to play a limited role in the disposition of paclitaxel, although their clinical significance in other ethnic populations remains to be investigated.