Advertisement

The role of ABCB1 polymorphism as a prognostic marker for primary central nervous system lymphoma

  • Ting Wu
  • Hui Kang
  • Dongxiao Zhuang
  • Yan Ma
  • Zhiguang Lin
  • Dina Suolitiken
  • Bobin ChenEmail author
  • Xiaoping XuEmail author
Original Article

Abstract

To investigate the possible role of functional single nucleotide polymorphism (SNP) in circadian genes as prognostic markers of primary central nervous system lymphoma (PCNSL). We conducted a prospective study using data from Huashan Hospital 2006–2015 and followed up 91 PCNSL patients until June 30, 2016. The survival of patients with different prognostic factors was compared by log-rank test. Univariate and multivariate analyses were performed by Cox regression. During a long-term follow-up (6–110 months), overall survival (OS) was 32 months (95% CI, 13.3–91.1) and progression-free survival (PFS) was 23 months (95% CI, 9.0–41.0) for the entire cohort. Age (P = 0.046, P = 0.001) and performance status (PS) score (P = 0.013, P = 0.003) showed differences in OS and PFS. ABCB1 rs1045642 variant showed significant difference in PFS between patients with CC genotype and those with CT/TT genotypes (P = 0.020). In multivariate analysis, age (HR = 2.3; 95% CI, 1.2–4.2, P = 0.008), PS (HR = 2.4; 95% CI, 1.3–4.4, P = 0.007), and ABCB1 rs1045642 (HR = 1.9; 95% CI, 1.0–3.3, P = 0.036) were the independent risk factors for PFS. In our results, the most important prognostic factors associated with higher risk of progression were ABCB1 rs1045642 CC genotype, PS > 2, and older age.

Keywords

ABCB1 gene Primary central nervous system lymphoma Single nucleotide polymorphism Prognostic factors 

Abbreviations

PCNSL

primary central nervous system lymphoma

NHL

non-Hodgkin lymphoma

DLBCL

diffuse large B cell lymphomas

SNP

single nucleotide polymorphism

OS

overall survival

PFS

progression-free survival

PS

performance status

CSF

cerebrospinal fluid

HD-MTX

high-dose methotrexate

WBRT

whole-brain radiotherapy

R

rituximab

IDA

idarubicin

Vm26

teniposide

FDG-PET

18F-2-fluoro-2-deoxy-d-glucose positron emission tomography

MRI

magnetic resonance imaging

LDH

lactate dehydrogenase

β2-MG

β2-microglobulin

ALL

acute lymphoblastic leukemia

Notes

Authors’ contributions

Bobin Chen, Hui Kang, and Xiaoping Xu designed the research. Hui Kang, Dongxiao Zhuang, and Dina Suolitiken collected the clinical data. Ting Wu, Hui Kang, Yan Ma, and Zhiguang Lin performed the research. Ting Wu analyzed the data and wrote the manuscript. All authors read and approved the final manuscript.

Funding information

This research was supported/funded by the Chinese Medicine Scientific Research Foundation of Shanghai Municipal Commission of Health and Family Planning (Grant No. 2014JP003A), the Science and Technology Development Fund of Bao Shan District (Grant No. 13-E-34), and the Shanghai Hospital Development Center (Grant No.16CR2043B).

Compliance with ethical standards

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Huashan Hospital. Written informed consent was obtained from the patients.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Supplementary material

277_2019_3629_MOESM1_ESM.pdf (367 kb)
ESM 1 (PDF 366 kb)

References

  1. 1.
    Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro-Oncology 14(Suppl 5):v1–v49.  https://doi.org/10.1093/neuonc/nos218 CrossRefGoogle Scholar
  2. 2.
    Camilleri-Broet S, Criniere E, Broet P, Delwail V, Mokhtari K, Moreau A, Kujas M, Raphael M, Iraqi W, Sautes-Fridman C, Colombat P, Hoang-Xuan K, Martin A (2006) A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases. Blood 107(1):190–196.  https://doi.org/10.1182/blood-2005-03-1024 CrossRefGoogle Scholar
  3. 3.
    Carbone A, Gloghini A, Larocca LM, Capello D, Pierconti F, Canzonieri V, Tirelli U, Dalla-Favera R, Gaidano G (2001) Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus-related lymphomas. Blood 97(3):744–751CrossRefGoogle Scholar
  4. 4.
    Kreher S, Johrens K, Strehlow F, Martus P, Borowiec K, Radke J, Heppner F, Roth P, Thiel E, Pietsch T, Weller M, Korfel A (2015) Prognostic impact of B-cell lymphoma 6 in primary CNS lymphoma. Neuro-Oncology 17(7):1016–1021.  https://doi.org/10.1093/neuonc/nov046 CrossRefGoogle Scholar
  5. 5.
    Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, Calderoni A, Rossi A, Vavassori V, Conconi A, Devizzi L, Berger F, Ponzoni M, Borisch B, Tinguely M, Cerati M, Milani M, Orvieto E, Sanchez J, Chevreau C, Dell’Oro S, Zucca E, Cavalli F (2003) Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 21(2):266–272CrossRefGoogle Scholar
  6. 6.
    Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, Schultz C, Leibel S, Nelson D, Mehta M, DeAngelis LM (2006) Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 24(36):5711–5715.  https://doi.org/10.1200/jco.2006.08.2941 CrossRefGoogle Scholar
  7. 7.
    Roth P, Keller A, Hoheisel JD, Codo P, Bauer AS, Backes C, Leidinger P, Meese E, Thiel E, Korfel A, Weller M (2015) Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients. Eur J Cancer 51(3):382–390.  https://doi.org/10.1016/j.ejca.2014.10.028 CrossRefGoogle Scholar
  8. 8.
    Mao X, Sun Y, Tang J (2014) Serum miR-21 is a diagnostic and prognostic marker of primary central nervous system lymphoma. Neurol Sci 35(2):233–238.  https://doi.org/10.1007/s10072-013-1491-9 CrossRefGoogle Scholar
  9. 9.
    Kasenda B, Haug V, Schorb E, Fritsch K, Finke J, Mix M, Hader C, Weber WA, Illerhaus G, Meyer PT (2013) 18F-FDG PET is an independent outcome predictor in primary central nervous system lymphoma. J Nucl Med 54(2):184–191.  https://doi.org/10.2967/jnumed.112.108654 CrossRefGoogle Scholar
  10. 10.
    Lee KM, Lan Q, Kricker A, Purdue MP, Grulich AE, Vajdic CM, Turner J, Whitby D, Kang D, Chanock S, Rothman N, Armstrong BK (2007) One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia. Hum Genet 122(5):525–533.  https://doi.org/10.1007/s00439-007-0431-2 CrossRefGoogle Scholar
  11. 11.
    Wang SS, Maurer MJ, Morton LM, Habermann TM, Davis S, Cozen W, Lynch CF, Severson RK, Rothman N, Chanock SJ, Hartge P, Cerhan JR (2009) Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma and follicular lymphoma. Leukemia 23(3):596–602.  https://doi.org/10.1038/leu.2008.240 CrossRefGoogle Scholar
  12. 12.
    Al-Dayel F, Al-Rasheed M, Ibrahim M, Bu R, Bavi P, Abubaker J, Al-Jomah N, Mohamed GH, Moorji A, Uddin S, Siraj AK, Al-Kuraya K (2008) Polymorphisms of drug-metabolizing enzymes CYP1A1, GSTT and GSTP contribute to the development of diffuse large B-cell lymphoma risk in the Saudi Arabian population. Leuk Lymphoma 49(1):122–129.  https://doi.org/10.1080/10428190701704605 CrossRefGoogle Scholar
  13. 13.
    Gra OA, Glotov AS, Nikitin EA, Glotov OS, Kuznetsova VE, Chudinov AV, Sudarikov AB, Nasedkina TV (2008) Polymorphisms in xenobiotic-metabolizing genes and the risk of chronic lymphocytic leukemia and non-Hodgkin’s lymphoma in adult Russian patients. Am J Hematol 83(4):279–287.  https://doi.org/10.1002/ajh.21113 CrossRefGoogle Scholar
  14. 14.
    Morton LM, Schenk M, Hein DW, Davis S, Zahm SH, Cozen W, Cerhan JR, Hartge P, Welch R, Chanock SJ, Rothman N, Wang SS (2006) Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma. Pharmacogenet Genomics 16(8):537–545.  https://doi.org/10.1097/01.fpc.0000215071.59836.29 CrossRefGoogle Scholar
  15. 15.
    Cerhan JR, Habermann TM, Maurer MJ, Wooldridge JE, Ansell SM, Nowakowski GS, Micallef IN, Thompson CA, Wang AH, Macon WR, Syrbu SI, Slager SL, Witzig TE, Link B (2010) Genetic polymorphisms in genes involved in R-CHOP metabolism and event-free and overall survival in diffuse large B-cell lymphoma. Blood 116(21):439–439Google Scholar
  16. 16.
    Chen BB, Xu XP, Shen L, Han TJ, Lin ZG, Chen Z, Kang H, Huang B, Lin GW (2013) Prognostic value of clinical characteristics and immunophenotypic biomarkers in 115 patients with primary central nervous system lymphoma. Chin Med J 126(3):482–487Google Scholar
  17. 17.
    Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science (New York, NY) 323(5922):1718–1722.  https://doi.org/10.1126/science.1168750 CrossRefGoogle Scholar
  18. 18.
    Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM (2007) A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science (New York, NY) 315(5811):525–528.  https://doi.org/10.1126/science.1135308 CrossRefGoogle Scholar
  19. 19.
    Bogacz A, Mrozikiewicz PM, Deka-Pawlik D, Seremak-Mrozikiewicz A, Bartkowiak-Wieczorek J, Barlik M, Drews K, Kowalska A, Grzeskowiak E (2013) Frequency of G2677T/A and C3435T polymorphisms of MDR1 gene in preeclamptic women. Ginekol Pol 84(9):781–787CrossRefGoogle Scholar
  20. 20.
    Vinolas N, Provencio M, Reguart N, Cardenal F, Alberola V, Sanchez-Torres JM, Baron FJ, Cobo M, Maestu I, Moreno I, Mesia C, Izquierdo A, Felip E, Lopez-Brea M, Marquez A, Sanchez-Ronco M, Taron M, Santarpia MC, Rosell R (2011) Single nucleotide polymorphisms in MDR1 gen correlates with outcome in advanced non-small-cell lung cancer patients treated with cisplatin plus vinorelbine. Lung Cancer (Amsterdam, Netherlands) 71(2):191–198.  https://doi.org/10.1016/j.lungcan.2010.05.005 CrossRefGoogle Scholar
  21. 21.
    Ma CX, Sun YH, Wang HY (2015) ABCB1 polymorphisms correlate with susceptibility to adult acute leukemia and response to high-dose methotrexate. Tumour Biol 36(10):7599–7606.  https://doi.org/10.1007/s13277-015-3403-5 CrossRefGoogle Scholar
  22. 22.
    Li Y, Yan PW, Huang XE, Li CG (2011) MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. Asian Pac J Cancer Prev 12(9):2405–2409Google Scholar
  23. 23.
    Wang Z, Wang T, Bian J (2013) Association between MDR1 C3435T polymorphism and risk of breast cancer. Gene 532(1):94–99.  https://doi.org/10.1016/j.gene.2013.09.050 CrossRefGoogle Scholar
  24. 24.
    Ni Y, Yin G, Xiao Z, Fan L, Wang L, Wu Y, Wu H, Qian S, Xu W, Li J, Miao K, Qiu H (2016) MDR1 polymorphisms have an impact on the prognosis of Chinese diffuse large B cell lymphoma patients. Tumour Biol 37(1):1237–1244.  https://doi.org/10.1007/s13277-015-3930-0 CrossRefGoogle Scholar
  25. 25.
    Gregers J, Green H, Christensen IJ, Dalhoff K, Schroeder H, Carlsen N, Rosthoej S, Lausen B, Schmiegelow K, Peterson C (2015) Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia. Pharmacogenomics J 15(4):372–379.  https://doi.org/10.1038/tpj.2014.81 CrossRefGoogle Scholar
  26. 26.
    Yang YL, Lin DT, Chang SK, Lin SR, Lin SW, Chiou RJ, Yen CT, Lin KH, Jou ST, Lu MY, Chang HH, Chang WH, Lin KS, Hu CY (2010) Pharmacogenomic variations in treatment protocols for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 54(2):206–211.  https://doi.org/10.1002/pbc.22292 Google Scholar
  27. 27.
    Rao DN, Anuradha C, Vishnupriya S, Sailaja K, Surekha D, Raghunadharao D, Rajappa S (2010) Association of an MDR1 gene (C3435T) polymorphism with acute leukemia in India. Asian Pac J Cancer Prev 11(4):1063–1066Google Scholar
  28. 28.
    Jamroziak K, Mlynarski W, Balcerczak E, Mistygacz M, Trelinska J, Mirowski M, Bodalski J, Robak T (2004) Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemia. Eur J Haematol 72(5):314–321.  https://doi.org/10.1111/j.1600-0609.2004.00228.x CrossRefGoogle Scholar
  29. 29.
    Kishi S, Cheng C, French D, Pei D, Das S, Cook EH, Hijiya N, Rizzari C, Rosner GL, Frudakis T, Pui CH, Evans WE, Relling MV (2007) Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood 109(10):4151–4157.  https://doi.org/10.1182/blood-2006-10-054528 CrossRefGoogle Scholar
  30. 30.
    Suthandiram S, Gan GG, Zain SM, Bee PC, Lian LH, Chang KM, Ong TC, Mohamed Z (2014) Effect of polymorphisms within methotrexate pathway genes on methotrexate toxicity and plasma levels in adults with hematological malignancies. Pharmacogenomics 15(11):1479–1494.  https://doi.org/10.2217/pgs.14.97 CrossRefGoogle Scholar
  31. 31.
    Dervieux T, Greenstein N, Kremer J (2006) Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum 54(10):3095–3103.  https://doi.org/10.1002/art.22129 CrossRefGoogle Scholar
  32. 32.
    Organista-Nava J, Gomez-Gomez Y, Saavedra-Herrera MV, Rivera-Ramirez AB, Teran-Porcayo MA, Alarcon-Romero Ldel C, Illades-Aguiar B, Leyva-Vazquez MA (2010) Polymorphisms of the gamma-glutamyl hydrolase gene and risk of relapse to acute lymphoblastic leukemia in Mexico. Leuk Res 34(6):728–732.  https://doi.org/10.1016/j.leukres.2009.11.027 CrossRefGoogle Scholar
  33. 33.
    Garcia-Bournissen F, Moghrabi A, Krajinovic M (2007) Therapeutic responses in childhood acute lymphoblastic leukemia (ALL) and haplotypes of gamma glutamyl hydrolase (GGH) gene. Leuk Res 31(7):1023–1025.  https://doi.org/10.1016/j.leukres.2006.08.007 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Hematology, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  2. 2.Department of Neurologic Surgery, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina

Personalised recommendations