Association of SLC22A1,SLCO1B3 Drug Transporter Polymorphisms and Smoking with Disease Risk and Cytogenetic Response to Imatinib in Patients with Chronic Myeloid Leukemia.

Abstract

OBJECTIVE\nTo determine whether polymorphisms of SLC22A1 and SLCO1B3 genes could predict imatinib (IM) response and chronic myeloid leukemia (CML) risk.\n\n\nMETHODS\nWe genotyped SLC22A1 (c.480G\u2005>\u2005C, c.1222A\u2005>\u2005G) and SLCO1B3 (c.334T\u2005>\u2005G, c.699G\u2005>\u2005A) polymorphisms in 132 patients with CML and 109 sex- and age-matched healthy subjects. The patients were evaluated for cytogenetic response by standard chromosome banding analysis (CBA).\n\n\nRESULTS\nPolymorphism analysis showed significant increased risk of IM resistance for SLC22A1c.1222AG (P\u2005=\u2005.03; OR\u2005=\u20052.2), SLCO1B3c.334TT/TG genotypes (P\u2005=\u2005.007; OR\u2005=\u20054.37) and 334T allele (P\u2005=\u2005.03; OR\u2005=\u20052.86). The double combinations of SLC22A1c.480CC and c.1222AG polymorphisms with SLCO1B3c.334TT/TG were significantly associated with complete cytogenetic response (CCyR) (P\u2005<.05; OR>\u20057). The interaction between all polymorphisms and smoking were associated with CML development and IM resistance (P\u2005≤.04; OR>\u20053).\n\n\nCONCLUSIONS\nOur study results suggest the influence of SLC22A1 and SLCO1B3 polymorphisms and the interaction of smoking on CML development and IM response.