MDR1 polymorphisms Have an Impact on the Prognosis of Chinese Diffuse Large B Cell Lymphoma Patients

MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP) dependent efflux transporter that plays a fundamental role of transport harmful compounds outside cells to maintain optimal health. The present study 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; HR=0.1, 95% 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 were significantly younger than the other genotypes (51.1±12.6 years 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. These results could provide evidence that the MDR1 SNPs may influence the biologic feature and prognosis of DLBCL and shade new lights in disease association studies.