Effects of Genetic Polymorphisms in the ABCB1 Gene onClinical Outcomes in Patients with Gastric Cancer Treated bySecond-line Chemotherapy

Abstract

<br/><b>Objective</b>: Tumor cells that overexpress P-glycoprotein (Pgp) may be resistant to several anticancer agentsdue to altered pharmacokinetics and reduced intracellular concentrations of the anticancer agents. Pgp is encodedby the ATP binding cassette gene B1 (ABCB1). To our knowledge, only one previous report has evaluated theeffect of ABCB1 gene polymorphisms on clinical outcomes of gastric cancer. The purpose of this analysis was toevaluate the impact of genetic polymorphisms of the ABCB1 gene on clinical outcomes in patients with advancedgastric cancer (AGC) treated with second-line chemotherapy. <br/><b>Methods</b>: We retrospectively analyzed the impactof ABCB1 gene polymorphisms (ABCB1 3435C>T) on clinical outcomes in 100 patients with AGC who receivedsecond-line chemotherapy. <br/><b>Results</b>: Median overall survival (OS) since the initiation of second-line chemotherapywas 6.0 months (95% confidence interval [CI], 4.8 to 8.0 months), and median progression-free survival (PFS)was 2.7 months (95% CI, 2.1 to 3.4 months). In a multivariate analysis of PFS, a 3435 CC polymorphism (n =45) was significantly associated with longer PFS compared with the CT/TT type polymorphism (n = 55), withborderline significance (PFS of 3.2 months vs. 2.2 months, respectively; HR 1.50; 95% CI, 0.98-2.30; P = 0.061).ABCB1 3435 C>T polymorphisms were not associated with OS. No interaction was seen between ABCB1polymorphisms and treatment regimens. <br/><b>Conclusion</b>: Genetic polymorphisms of ABCB1 3435C>T might havea possible impact on clinical outcomes of second-line chemotherapy in AGC. Further prospective evaluationusing a larger sample size is required.