Original Article MDR1 polymorphisms are associated with sensitivity to platinum-based chemotherapy in gastric cancer
Int J Clin Exp Pathol
Objective: The study aimed to investigate the relationship of multidrug resistance gene 1 (MDR1) C1236T, G2677T/A and C3435T polymorphisms with sensitivity to platinum-based chemotherapy in gastric cancer. Methods: 96 patients who had experienced 6 months of platinum-based chemotherapy after the first operation were collected in the study. The genotypes of MDR1 C1236T, G2677T/A and C3435T loci in peripheral blood from all subjects were tested by matrix assisted laser desorption ionization-time
... on ionization-time of flight (MALDI-TOF) mass spectrometry. Haploview 4.2 software was utilized to analyze the linkage disequilibrium and haplotypes of MDR1 polymorphisms. Odds ratio and 95% confidence interval (CI), calculated by χ 2 test, represent the relation of MDR1 polymorphisms with sensitivity to chemotherapy. Results: The sensitivity to platinum-based therapy of each patient was evaluated, so the patients were divided into two groups: sensitivity and resistance groups. In the analysis, TT genotype of 1236C/T was significantly correlated with enhanced sensitivity to platinum-based therapy (OR: 0.21, 95% CI: 0.05-0.88). Among the genotypes of G2677T/A polymorphism, TA appeared to increase the sensitivity to the therapy (OR: 7.22, 95% CI: 1.08-48.48). As for C3435T, TT genotype carriers exhibited higher sensitivity to platinum therapy compared to CC (OR: 2.83, 95% CI: 1.05-7.66). Only the haplotypes with frequencies more than 5% were analyzed, in which TTT hap-lotype showed strong association with sensitivity to platinum therapy (OR: 3.52, 95% CI: 1.07-11.58). Conclusion: MDR1 C1236T, G2677T/A and C3435T polymorphisms may be related to the sensitivity to platinum-based chemo-therapy in gastric cancer.