Association of the ABCB1 3435C>T polymorphism and treatment outcomes in advanced gastric cancer patients treated with paclitaxel-based chemotherapy.

Abstract

We evaluated the frequency of ABCB1 polymorphisms (2677G/T>A and 3435C>T) and studied the association between the polymorphisms and clinical outcomes of paclitaxel-based chemotherapy in advanced gastric cancer patients. This study was performed in 43 gastric cancer patients and a control group consisting of 118 healthy volunteers. Patients were treated with paclitaxel combined with an infusional 5-fluorouracil and low-dose leucovorin. Genomic DNA from peripheral blood mononuclear cells was used to determine ABCB1 polymorphisms by direct sequencing. Genotypes were investigated for their association with survival and toxicity. The ABCB1 3435 C allele was more frequent in gastric cancer patients than healthy volunteers (p<0.001). The 2677G>T/A and 3435C>T polymorphisms were independent factors associated with shorter progression-free survival (PFS) (p=0.024, p=0.001, respectively). In combined analysis of 2677 and 3435 polymorphisms, the 3435C>T polymorphism was an independent factor for poor PFS (p=0.01). The 3435CT and TT genotypes were associated with mucositis (p=0.04), and the variant genotypes at 2677 loci were associated with diarrhea (p=0.034). Our data suggest that the ABCB1 polymorphism at 3435 is associated with clinical outcomes after paclitaxel-based combined chemotherapy in advanced gastric cancer patients.