MDR1 (C3435T) polymorphism: relation to the risk of breast cancer and therapeutic outcome

P-glycoprotein (PGP), the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of carcinogens and cytostatics. It has been suggested that MDR1 polymorphisms contribute to the variability in cancer risk and therapeutic outcome. We examined the relevance of C3435T polymorphism in relation to breast cancer susceptibility, clinical and pathological characteristics of breast carcinoma, the therapeutic response and hematologic toxicities after anthracycline-based chemotherapy. A significant association between allele frequencies and histological type, stage and histological grade was observed (P = 0.024, 0.014, 0.006, respectively, chi(2)-test or Fisher's exact test). We also found significantly higher (P = 0.019, chi(2)-test) T allele frequency in breast cancer patients (n = 221) than in controls (n = 113). A significantly enhanced therapeutic outcome after neoadjuvant therapy (n = 38; P = 0.021, Fisher's exact test) and longer time to progression after anthracycline-based chemotherapy (n = 102; P = 0.049, log-rank test) were observed in CC homozygotes. However, no significant association between hematologic toxicities and C3435T polymorphism was detectable. The Pharmacogenomics Journal (2010) 10, 62-69; doi: 10.1038/tpj.2009.41; published online 15 September 2009