ABCB1 variants (C1236T, rs1128503 and G2677T/A, rs2032582) do not show an association with recurrence and survival in patients with breast cancer undergoing anthracycline-based chemotherapy

Abstract

Breast cancer (BC) is the second most prevalent type of cancer worldwide and the most common among women. Also, BC shows different subtypes and patterns of chemotherapy response. Moreover, BC recurrence pattern is not well knowledge. But, genetic variants can alter drug pharmacokinetics and pharmacodynamics with an impact in treatment outcome. In many drugs in use, drug carriers act on drug absorption, distribution and elimination. ABCB1 encodes the P-glycoprotein – membrane transport protein – responsible for the cellular efflux of drugs, xenobiotics, cellular metabolites and anticancer agents, being crucial in response to chemotherapy. Our aim was to determine whether C1236T (rs1128503) and G2677 T/A (rs2032582) variants in the ABCB1 were associated with recurrence and survival in patients with BC, with invasive ductal carcinoma, treated with anthracycline-based chemotherapy. The study enrolled 146 patients with BC and 609 healthy control subjects. Genotyping in BC cases was performed by allele-specific PCR. The disease-free survival and overall survival analysis was performed by SPSS software. The χ2, Fisher's exact, univariate and multivariate logistic regression tests were performed by SAS software. ABCB1 variants were in accordance to Hardy-Weinberg equilibrium [P-value>.05]: (C1236T) CC = 57(39.1%), CT = 64(43.8%), TT = 25(17.1%); (G2677 T/A) GG = 69(47.3%), GA = 63(43.1%), AA = 10(6.8%), GT = 2(1.4%), AT = 2(1.4%) in the group including patients with BC. However, in healthy controls concerning the G2677 T/A variant, the ABCB1 variant is not in accordance with the Hardy-Weinberg equilibrium [P-value<.05]. The association between ABCB1 variants and recurrence did not show statistical significance for univariate and multivariate models (P-value>.05). Also, the Kaplan-Meier analysis of disease-free survival and overall survival regarding ABCB1 variants did not show statistical significance (P-value>.05). In our sample of patients with BC treated with anthracycline-based chemotherapy, ABCB1 variants were not associated with recurrence, disease-free survival and overall survival.