Analysis of the Potential Associations of Two Common Polymorphisms in the ABCC1 Three Prime Untranslated Region With Breast Cancer Susceptibility

Background: Multiple drug resistance in breast cancer patients is one of the most important problems when it comes to the treatment of this disease. In this regard, polymorphisms in DNA sequences play a key role in pharmacokinetics and pharmacodynamics. ABCC1 gene encodes the Multidrug Resistance-Associated Protein 1 (MRP1) protein, which transports many chemotherapy drugs or cellular physiological substances through the cell membrane. As a result, suppression, genetic variations and changes in the expression of this gene may change the drug’s distribution, cytotoxicity and clinical outcomes. Objectives: We performed this study to determine the prevalence of different variants of ABCC1 3’ untranslated region (UTR) single nucleotide polymorphisms (SNPs) (rs3743527 and rs129081) in breast cancer patients and healthy controls. Materials and Methods: We analyzed the prevalence of different alleles of these polymorphisms on DNA extracted from whole blood of 44 patients with breast cancer and 25 healthy controls. We checked C/G variants of rs129081 by performing nestedpolymerase chain reaction (PCR) and allele specific-polymerase chain reaction (AS-PCR). Analysis of C/T alleles in rs3743527 was done using PCR-restriction fragment length polymorphism (RFLP). The results were then confirmed by sequencing. Results: No significant correlation was seen in rs3743527 and rs129081 polymorphism’s allelic and genotypic frequencies between the patient group and control individuals (P value > 0.05). The average frequencies of rs129081 G and C alleles was 40 (58%) and 29 (42%), respectively. In our sample the average frequencies of rs3743527 C and T alleles, were 41 (61%) and 28 (39%), respectively. The results of chi-square test showed strong correlations between the incidences of various genotypes in both groups (P value = 0). On average, 27%, 26% and 16% of participants had genotype CC/GG, CT/CG and TT/CC, respectively. Conclusions: Taken together, distribution and frequencies of rs129081 and rs3743527 variants in the patient group and control individuals may not correlate with susceptibility to breast cancer; however, more detailed studies are needed to confirm these results.