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

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Tumor Biology

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.

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Acknowledgments

This study was supported by grants from National Natural Science Foundation of China (81470329), National Public Health Grand Research Foundation (No. 201202017), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institute (No. JX10231801), Program for Development of Innovative Research Teams in the First Affiliated Hospital of Nanjing Medical University, Project of National Key Clinical Specialty, National Science & Technology Pillar Program (No. 2014BAI09B12), and Project Funded by Jiangsu Provincial Special Program of Medical Science (No. BL2014086).

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    Authors and Affiliations

    1. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China

      Ying Ni, Guangli Yin, Zhengrui Xiao, Lei Fan, Li Wang, Yujie Wu, Hanxin Wu, Sixuan Qian, Wei Xu, Jianyong Li, Kourong Miao & Hairong Qiu

    2. Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China

      Ying Ni, Guangli Yin, Zhengrui Xiao, Lei Fan, Li Wang, Yujie Wu, Hanxin Wu, Sixuan Qian, Wei Xu, Jianyong Li, Kourong Miao & Hairong Qiu

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    Correspondence to Kourong Miao or Hairong Qiu.

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    Ying Ni and Guangli Yin contributed equally to this work.

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    Ni, Y., Yin, G., Xiao, Z. et al. MDR1 polymorphisms have an impact on the prognosis of Chinese diffuse large B cell lymphoma patients. Tumor Biol. 37, 1237–1244 (2016). https://doi.org/10.1007/s13277-015-3930-0

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