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 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.
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Ying
Y
Ni
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Guangli
G
Yin
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Zhengrui
Z
Xiao
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Lei
L
Fan
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Li
L
Wang
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Yujie
Y
Wu
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Hanxin
H
Wu
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Sixuan
S
Qian
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Wei
W
Xu
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China.
Jianyong
J
Li
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China. kourongmiao@163.com.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China. kourongmiao@163.com.
Kourong
K
Miao
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China. qiuqiu1203@sina.com.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China. qiuqiu1203@sina.com.
Hairong
H
Qiu
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000368:Aged; D000483:Alleles; D044466:Asian People; D002681:China; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B
Diffuse large B cell lymphoma (DLBCL); Multidrug resistance 1 (MDR1); Polymorphism; Prognosis