The Relationship of ABCB1/MDR1 and CYP1A1 Variants with the Risk of Disease Development and Shortening of Overall Survival in Patients with Multiple Myeloma

被引:3
|
作者
Zmorzynski, Szymon [1 ]
Wojcierowska-Litwin, Magdalena [1 ]
Popek-Marciniec, Sylwia [1 ]
Szudy-Szczyrek, Aneta [2 ]
Styk, Wojciech [3 ]
Chocholska, Sylwia [2 ]
Filip, Agata Anna [1 ]
机构
[1] Med Univ Lublin, Dept Canc Genet, Cytogenet Lab, PL-20059 Lublin, Poland
[2] Med Univ Lublin, Chair & Dept Hematooncol & Bone Marrow Transplant, PL-20059 Lublin, Poland
[3] Warsaw Management Univ, Inst Pedag & Psychol, Dept Psychol, PL-03772 Warsaw, Poland
关键词
multiple myeloma; genetic variants; polymorphisms; ABCB1; gene; CYP1A1; PROTEASOME INHIBITOR BORTEZOMIB; MULTIDRUG-RESISTANCE GENE; CANCER RISK; C3435T POLYMORPHISM; MDR1; ACTIVATION; EXPRESSION; SUSCEPTIBILITY; IDENTIFICATION; MANAGEMENT;
D O I
10.3390/jcm10225276
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
(1) Background: The aim of our study was to analyze the possible relationship of ABCB1 and CYP1A1 gene variants with susceptibility and outcome of multiple myeloma (MM); (2) Methods: Genomic DNA samples from 110 newly-diagnosed MM patients and 100 healthy blood donors were analyzed by methods-PCR-RFLP (for ABCB1 3435C > T, CYP1A1 6235T > C-m1), automated DNA sequencing (for ABCB1 1236C > T, 2677G > T/A) and allele-specific PCR (for CYP1A1 4889A > G-m2); (3) Results: The genotypic frequencies of CYP1A1 4889A > G variant were not in Hardy-Weinberg equilibrium for MM patients. The presence of ml and m2 CYP1A1 alleles decreased the risk of MM-OR = 0.49 (p = 0.011) and OR = 0.27 (p = 0.0003), respectively. In turn, TT genotype (ABCB1 2677G > T/A) increased the risk of this disease (p = 0.007). In the multivariate Cox analysis CT + TT genotypes (ABCB1 3435C > T) were associated with decreased risk of death (HR = 0.29, p = 0.04). In log-rank test in patients with CT genotype (ABCB1 3435C > T) was observed association of overall survival with the type of treatment; (4) Conclusions: Our findings suggest that T-alleles of ABCB1 2677G > T/A and m1 /m2 alleles of CYP1A1 affected the susceptibility of MM. Moreover, T-allele of ABCB1 3435C > T might be independent positive prognostic factor in MM.
引用
收藏
页数:21
相关论文
共 50 条
  • [41] Influence of ABCB1 polymorphisms on the pharmacokinetics and toxicity of lenalidomide in patients with multiple myeloma
    Takahiro Kobayashi
    Masatomo Miura
    Maiko Abumiya
    Yumiko Akamine
    Fumiko Ito
    Naoto Takahashi
    Medical Oncology, 2019, 36
  • [42] Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene
    Kroetz, DL
    Pauli-Magnus, C
    Hodges, LM
    Huang, CC
    Kawamoto, M
    Johns, SJ
    Stryke, D
    Ferrin, TE
    DeYoung, J
    Taylor, T
    Carlson, EJ
    Herskowitz, I
    Giacomini, KM
    Clark, AG
    PHARMACOGENETICS, 2003, 13 (08): : 481 - 494
  • [43] Complete Knockout of Endogenous Mdr1 (Abcb1) in MDCK Cells by CRISPR-Cas9
    Simoff, Ivailo
    Karlgren, Maria
    Backlund, Maria
    Lindstrom, Anne-Christine
    Gaugaz, Fabienne Z.
    Matsson, Par
    Artursson, Per
    JOURNAL OF PHARMACEUTICAL SCIENCES, 2016, 105 (02) : 1017 - 1021
  • [44] Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene (MDR1, ABCB1)
    Hitzl, M
    Schaeffeler, E
    Hocher, B
    Slowinski, T
    Halle, H
    Eichelbaum, M
    Kaufmann, P
    Fritz, P
    Fromm, MF
    Schwab, M
    PHARMACOGENETICS, 2004, 14 (05): : 309 - 318
  • [45] MDR1 diplotypes as prognostic markers in multiple myeloma
    Maggini, Valentina
    Buda, Gabriele
    Martino, Alessandro
    Presciuttini, Silvano
    Galimberti, Sara
    Orciuolo, Enrico
    Barale, Roberto
    Petrini, Mario
    Rossi, Anna Maria
    PHARMACOGENETICS AND GENOMICS, 2008, 18 (05) : 383 - 389
  • [46] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents
    Woodahl, Erica L.
    Crouthamel, Matthew H.
    Bui, Tot
    Shen, Danny D.
    Ho, Rodney J. Y.
    CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2009, 64 (01) : 183 - 188
  • [47] The importance of C1236T polymorphism in the ABCB1/MDR1 gene in assessment of susceptibility to inflammatory bowel diseases in the Polish population
    Dudarewicz, Michal
    Baranska, Malgorzata
    Rychlik-Sych, Mariola
    Trzcinski, Radzislaw
    Dziki, Adam
    Skretkowicz, Jadwiga
    PRZEGLAD GASTROENTEROLOGICZNY, 2013, 8 (01): : 38 - 43
  • [48] First report on the distribution of 3435C>T ABCB1/MDR1 polymorphism in healthy Bosniak population
    Adler, Grazyna
    Pawinska-Matecka, Anna
    Garstka, Agnieszka
    Salkic, Nermin Nusret
    Valjevac, Amina
    Karakiewicz, Beata
    TURKISH JOURNAL OF MEDICAL SCIENCES, 2016, 46 (03) : 942 - 944
  • [49] Genetic Variability and Haplotype Profile of MDR1 (ABCB1) in Roma and Hungarian Population Samples with a Review of the Literature
    Sipeky, Csilla
    Csongei, Veronika
    Jaromi, Luca
    Safrany, Eniko
    Maasz, Anita
    Takacs, Istvan
    Beres, Judit
    Fodor, Lajos
    Szabo, Melinda
    Melegh, Bela
    DRUG METABOLISM AND PHARMACOKINETICS, 2011, 26 (02) : 206 - 215
  • [50] Association of the MDR1 (ABCB1) gene 3435C>T polymorphism with male infertility
    Drozdzik, Marek
    Stefankiewicz, Joanna
    Kurzawa, Rafal
    Gornik, Wanda
    Baczkowski, Tomasz
    Kurzawski, Mateusz
    PHARMACOLOGICAL REPORTS, 2009, 61 (04) : 690 - 696