MDR1 Single Nucleotide Polymorphism G2677T/A and Haplotype Are Correlated with Response to Docetaxel-Cisplatin Chemotherapy in Patients with Non-Small-Cell Lung Cancer.

Background: The multidrug resistance gene 1 (MDR1) encodes P-glycoprotein (P-gp), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. MDR1 gene polymorphisms may have an impact on the expression and function of P-gp, thereby influencing the response to chemotherapy. Objectives: To investigate whether the MDR1 2677 and 3435 genotypes are associated with the sensitivity of non-small-cell lung cancer (NSCLC) to docetaxel. Methods: In this study we investigated the potential association of MDR1 2677G>T at exon 21, 3435C>T at exon 26 and their haplotypes with chemotherapy response of 54 Han Chinese patients with NSCLC. The patients were treated with docetaxel-cisplatin. Results: The 2677 GG genotype was associated with a significantly better response to chemotherapy compared with the combined 2677 GT and TT genotype (p = 0.035). The 3435 CC genotype was also associated with a better response to chemotherapy compared with the combined 3435 CT and TT genotypes although the difference was not statistically significant (p = 0.123). Moreover, 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). Conclusion: Our findings suggest that the MDR1 2677G>T/A polymorphism and the 2677G-3435C haplotype are predictors of treatment response to docetaxel-cisplatin chemotherapy in NSCLC patients. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]