No abstract

The human multidrug resistance gene 1 (MDR1) encodes a plasma membrane, P-glycoprotein (Pgp), which functions as the transmembrane efflux pump for various structurally unrelated anticancer agents and toxins. Polymorphisms in the MDR1 gene may have an impact on the expression and function of Pgp, thereby influencing the susceptibility to various diseases, including cancer. Recently, a silent C3435T polymorphism in exon 26 of MDR1 has been reported to be associated with decreased expression of Pgp in TT genotype carriers and thus it may alter the physiological protective role of Pgp and influence disease risk. To evaluate the association of this polymorphism with breast cancer, 106 patients with breast cancer and 77 healthy controls were enrolled in this study. They were visited at two centers during a 1-year period (2006-2007). Data about the risk factors of breast cancer were collected using questionnaires. DNA of the whole-blood sample was extracted, and the polymorphic fragment was amplified by polymerase chain reaction using specific primers. The C3435T polymorphism was detected by the restriction fragment length polymorphism method. There were no significant differences in genotype (p = 0.744) and allele (p = 0.590) frequencies between patients and control subjects. Moreover, distribution of the breast cancer patients' risk factors was not different among CC, CT, and TT genotypes. Our results suggest that C3435T MDR1 polymorphism was not associated with the susceptibility to breast cancer in the population studied.

The human multidrug resistance (MDR1) gene product P-glycoprotein is highly expressed in intestinal epithelial cells, where it constitutes a barrier against xenobiotics, bacterial toxins, drugs and other biologically active compounds, possibly carcinogens. In this study, an association of MDR1 gene polymorphism and the occurrence of colorectal cancer were evaluated. In this case-control-designed 118 unrelated colorectal cancer and 137 sex-and-ages matched healthy controls were enrolled. The C3435T MDR1 gene polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism method. Significantly increased frequencies of the 3435T allele and the 3435TT were observed in patients with colorectal cancer compared with controls (P = 0.03; OR, 95% CI; 1.46 for 3435T allele and P = 0.003; OR, 95% CI; 2.2 for 3435TT genotype). In contrast, frequency of genotype TT was significantly higher in controls compared to colorectal cancer (P = 0.006; OR, 95% CI; 0.49 for TC genotype). In this study suggest that C3435T MDR1 polymorphism has an association with colorectal cancer. The results support that the presence of allele C results in decreased susceptibility to colorectal cancer.