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International Journal of Pharmacology

Year: 2007  |  Volume: 3  |  Issue: 6  |  Page No.: 453 - 460

Polymorphic Sites (1236 and 3435) in Multi Drug Resistance Gene 1 Influencing Drug Response in Breast Cancer Patients

Shaswati Khan, Kaiser Jamil, G. Prabhavathy Das, Ch. Mohana Vamsy and Sudha Murthy

Abstract

This investigation analyzed the occurrences of polymorphisms (SNPs) in MDR1 gene at exon 12 (C1236T) and 26 (C3435T) individually and in combination in breast cancer patients and determined their possible associations to adjuvant chemotherapy. The study group included hundred primary invasive ductal carcinoma patients who subsequently received chemotherapy (the regimen generally consisted of commonly used drugs like adriamycin, cyclophosphamide, 5-fluorouracil and docetaxal and their combinations). Blood samples from 100 healthy individuals used as controls were also genotyped for the MDR1 gene. This investigation revealed a statistically significant correlation with response to various regimens of adjuvant chemotherapy showing a low response to therapy with CT/TT genotype at (exon 12) 1236 codon (p<0.001) and favorable response to therapy with CT/TT genotype (exon 26) at 3435 codon (p<0.001). The combined effect of both the exons, i.e., mutant exon 12 and wildtype 26 gave poor response, whereas the combination of mutated exon 26 and wildtype exon 12 gave favorable response to chemotherapy (p<0.0005). These findings demonstrate for the first time that polymorphisms in exon 12 and 26 of the MDR1 gene greatly influence the variations in drug response in patients.

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