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Poster 35. The role of multidrug resistance gene 1 (MDR1) in breast cancer resistance R. Vaclavikova1, S. Nordgard2, GA Alnaes2, M. Hubackova1, E. Kubala3, R. Kodet3, M. Mrhalova3, J. Novotny4, VN Kristensen2, I. Gut1 and P. Soucek1 1 National Institute of Public Health, Prague, Czech Republic; 2 Department of Genetics, Institute for Cancer Research, Oslo, Norway; 3 Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; 4 Department of Oncology, General Teaching Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic firstname.lastname@example.org Multidrug resistance of tumor cells to cytotoxic drugs is one of the major impediments in successful cancer chemotherapy. A significant part of tumor resistance to chemotherapy is caused by ABC transporter P-glycoprotein (P-gp, encoded by MDR1 gene). High expression of MDR1 and its genetic variations thus may have great clinical impact. Analyses of 6 MDR1 SNPs and expression in 90 sets of samples from breast cancer patients were performed. MDR1 genotype was assayed with a novel method that allows simultaneous assessment of multiple SNPs on a single Nanogen electronic microarray. MDR1 expression was quantified in cDNA samples from tumor and non-tumor tissues of breast cancer patients by real-time PCR. Two- sided t-test and Mann-Whitney U test were used for assessment of the effect of MDR1 polymorphisms on the MDR1 expression and for the analysis of associations with clinical and pathological characteristics. MDR1 was expressed in 87/88 (98.9 %) of tumor and in 39/40 (97.5%) of non-tumor samples. Striking inter-individual variability in expression of MDR1 was found. MDR1 was down-regulated in 89.7% of all tumors. No significant correlation was observed between MDR1 expression and any clinico-pathological data. High frequencies of variant alleles in MDR1 exon 12 (C1236T, q = 38.3) and exon 26 (C3435T, q = 54.0) were revealed in patients. Individuals with variant alleles in these SNPs had significantly lower MDR1 expression in their tumors than patients with normal genotype. SNPs in exon 12 and exon 26 also correlated with estrogen status of patients. Thus these SNPs may affect function of P-gp and modify breast cancer outcome. This work was supported by grant of GA CR 305/07/P347, IGA 8563-5 and Young Scientist Research Program of NIPH (Prague, Czech Republic).
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