MDR1 C3435T polymorphism in patients with breast cancer.

ABSTRACT

BACKGROUND: The human multidrug-resistant gene (MDR1) encodes P-glycoprotein (Pgp), a membrane-bound efflux transporter conferring resistance to a number of natural cytotoxic drugs and potentially toxic xenobiotics. Single-nucleotide polymorphisms (SNPs) in MDR1 gene are associated with phenotypic variation in Pgp expression levels of tissue. SNPs may alter the physiological protective role of Pgp and, therefore, influence disease risk. METHODS: In our study we identified the MDR1 C3435T polymorphism in breast cancer patients (n = 57) and healthy subjects (n = 50). DNA was extracted from peripheral blood samples by standard phenol/chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of C3435T single nucleotide polymorphism. RESULTS: We obtained CC, CT and TT genotype frequencies in breast cancer patients as 12.3%, 57.9% and 29.8%, respectively. In the control group, frequencies of genotypes were found as 36% for CC, 46% for CT and 18% for TT. We observed difference in SNPs in MDR1 gene C3435T polymorphism between breast cancer patients and healthy controls (chi(2) = 8.66, df = 2, p = 0.013). The C allele frequency was found in 41.2% and the T allele frequency was found in 58.8%. C3435T MDR1 gene allele frequencies in breast cancer patients as compared to results in control group were as follows [OR = 1.5 (95% CI 1.09-1.96)]. In the patient group, T allele frequency was significantly higher than controls (p <0.01). Clinicopathological parameters of patients with breast cancer were compared for C3435T polymorphism. We did not find any significant difference between clinicopathological parameters and MDR1 phenotype of breast cancer patients. The progression-free survival rate in a subgroup analysis based on MDR1 genotypes with CC genotype was 71.4%, CT genotype was 75.7%, and TT genotype was 88.2%, respectively. This difference was not statistically significant (log rank p = 0.63). CONCLUSIONS: Results of the present study demonstrated a 1.5-fold increased risk for development of breast cancer in T allele carriers.