Association between SNPs C1236T and C3435T of the ABCB1 Gene and the Neoadjuvant Chemotherapy in Breast Cancer

Introduction: Breast cancer is the most common malignant tumor in women and the leading cause of cancer-related death among female populations worldwide. Neoadjuvant chemotherapy is a systematic treatment administered before radiotherapy or surgery. It remains a preferred treatment option in cancer management, given its relevant results. However, certain single-nucleotide polymorphisms (SNPs) of the MDR1 gene are cited as factors that can induce differences between individuals in response to neoadjuvant chemotherapy.

Objectives: The aim of this study was to evaluate the possible association between SNPs of the ABCB1 gene, specifically the polymorphisms C1236T and C3435T, and the response to neoadjuvant chemotherapy in Senegalese women with breast cancer.

Methods: Our study included 60 senegalese patients diagnosed with breast cancer and treated with four different neoadjuvant chemotherapy protocols (AC, FAC, CARBO and TXT). Wealso included 15 healthy women as a control group. The sample type was a cytological biopsy. The C1236T and C3435T polymorphisms were genotyped using the PCR-RFLP method with respectively the following primers 5′-TTTTTCTCACGGTCCTGGTAG-3′; 5′-CATCCCCTCTGTGGTCATA-3′; and 5CAAAGAAATAAAGC-3′; 5′-CTTACATTAGGCAGTGACT CG-3′. As for restriction enzymes, we used HaeIII for exon 12 and DpnII for exon 26. Genotypic data was recorded in an Excel spreadsheet, and the results were analyzed using R Studio software, version 3.4.2. The genotypic frequencies were determined using GenePop software, version 4.3. Linear regression tests were conducted to determine association between the MDR1 gene polymorphisms and neoadjuvant chemotherapy using XLSTAT software (Lumivero, 2023), version 2023.2.0 (1411).

Results: The CC genotype was found in a proportion of 58.3% for the C1236T SNP and 61.6% for the C3435T SNP. Healthy women were exclusively (100%) of the CC genotype for exons 12 and 26. The heterozygous CT genotype was not detected in any of the participants in our study. Linear regression tests mostly showed no association between chemotherapy protocols and the C1236T and C3435T polymorphisms of the ABCB1 gene. In the cases where the P-value was significant, the association was weak.

Conclusion: In the present study, no significant association was found between the C1236T and C3435T polymorphisms of the MDR1 gene and neoadjuvant chemotherapy regimens in Senegalese women with breast cancer.

Keywords: Breast Cancer, ABCB1, polymorphism, association, Senegal.