MDR1 polymorphisms have an impact on the prognosis of Chinese diffuse large B cell lymphoma patients

Abstract

MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP)-dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health. The present study was aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A, and C3435T were focused on, and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele-specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6 vs. 60.0 %, respectively; hazard ratio (HR) = 0.1, 95 % confidence interval (CI) 0.01-0.6, p = 0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7 vs. 51.9 %, respectively; p = 0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4 % in with T group vs. 73.7 % in without T group, respectively; HR = 1.9, 95 % CI 1.0-3.6, p = 0.045). At locus G2677T/A, the age for genotypes AG and AT groups was significantly younger than the other genotypes (51.1 ± 12.6 vs. 57.7 ± 13.4 years, respectively; p = 0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0 vs. 50.6 %, respectively; HR = 7.8, 95 % CI 1.9-32.6, p = 0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT + TT at locus C1236T, allele C, and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL.

Clinical relevance of multi-drug resistance gene C3435T polymorphism in diffuse large B-cell lymphoma in Xinjiang

“…This study suggested that none of the alleles and genotypes at MDR1 C3435T was associated with the response of DLBCL to R-CHOP regimen, which was consistent with the study of Nizar M Mhaidat et al [ 11 ] While the study of Ying Ni et al [ 15 ] showed that DLBCL patients carrying C allele achieved better efficacy ( P = .009), whose mechanism may be siRNA-mediated down-regulation of ABCB1 (MDR1), thereby leading to the accumulation of chemotherapeutic agents in tumor cells to induce apoptosis. [ 19 ] The inconsistency of results may be related to the different grouping of efficacy in study design.…”

“…The mechanism may be that molecules on the surface of tumor cells induce expression of G-protein-coupled receptors, which up-regulate the level of MDR1 and lead to the development of tumor drug resistance. [ 16 ] In contrast, the study of Ni Y et al [ 15 ] showed that C allele and CC genotype of C3435T were associated with a better prognosis in DLBCL. Our study did not get any statistically significant results.…”

“…This is consistent with 2 China's studies. [ 14 , 15 ] One study of central nervous system lymphoma in 91 cases in China [ 7 ] showed that patients carrying CC genotype were significantly associated with shorter PFS ( P = .020), indicating that CC genotype is an independent prognostic risk factor for CNS lymphoma. Another study [ 3 ] showed that CT genotype was associated with poor prognosis of childhood acute lymphoblastic leukemia.…”

Impact of ABCB1, ABCC1, ABCC2, and ABCG2 variants in predicting prognosis and clinical outcomes of north Indian lung cancer patients undergoing platinum‐based doublet chemotherapy

“…26 By contrast, some studies have shown that Chinese B cell lymphoma patients with the T allele of the ABCB1 C 1236 T polymorphism had an increased OS. 29 These discrepancies could be attributed to ethnicity, patient clinical features, and tumor histological heterogeneity, which could play an important role. However, many more studies are required to understand how the ABCB1 C 1236 T polymorphism affects MDR1 gene expression and its protein function.…”

Dysregulated MDR1 by PRDM1/Blimp1 Is Involved in the Doxorubicin Resistance of Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma

“…), were found to be significantly upregulated. Indeed, MDR1 has been indicated to predict a poor prognosis in patients with DLBCL [26, 27]. However, the reason MDR1 is overexpressed in tumor tissues of treated patients remains unclear.…”