BACKGROUND: The MDR1 gene encodes P-glycoprotein (PGP), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. Polymorphisms in the MDR1 gene may have an impact on the expression and function of PGP, thereby influencing the response to chemotherapy. METHODS: We investigated the potential association of MDR1 polymorphisms (2677G>T at exon 21 and 3435C>T at exon 26) and their haplotypes with chemotherapy response in 54 small cell lung cancer (SCLC) patients who received a combination chemotherapy of etoposide-cisplatin. RESULTS: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotype (P = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Consistent with the results of genotyping analyses, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (P = 0.015). CONCLUSIONS: Our findings suggest that the MDR1 2677G>T and 3435C>T polymorphisms can be used for predicting treatment response to etoposide-cisplatin chemotherapy in SCLC patients.
BACKGROUND: The MDR1 gene encodes P-glycoprotein (PGP), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. Polymorphisms in the MDR1 gene may have an impact on the expression and function of PGP, thereby influencing the response to chemotherapy. METHODS: We investigated the potential association of MDR1 polymorphisms (2677G>T at exon 21 and 3435C>T at exon 26) and their haplotypes with chemotherapy response in 54 small cell lung cancer (SCLC) patients who received a combination chemotherapy of etoposide-cisplatin. RESULTS: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotype (P = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Consistent with the results of genotyping analyses, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (P = 0.015). CONCLUSIONS: Our findings suggest that the MDR1 2677G>T and 3435C>T polymorphisms can be used for predicting treatment response to etoposide-cisplatin chemotherapy in SCLCpatients.
Authors: H H Yoon; P Catalano; M K Gibson; T C Skaar; S Philips; E A Montgomery; M J Hafez; M Powell; G Liu; A A Forastiere; A B Benson; L R Kleinberg; K M Murphy Journal: Cancer Chemother Pharmacol Date: 2011-02-01 Impact factor: 3.333
Authors: Grace K Dy; Sumithra J Mandrekar; Garth D Nelson; Jeffrey P Meyers; Araba A Adjei; Helen J Ross; Rafat H Ansari; Alan P Lyss; Philip J Stella; Steven E Schild; Julian R Molina; Alex A Adjei Journal: J Thorac Oncol Date: 2013-01 Impact factor: 15.609