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
  • [1] Polymorphisms and haplotypes in the multidrug resistance 1 gene (MDR1/ABCB1) and risk of multiple myeloma
    Jamroziak, Krzysztof
    Balcerczak, Ewa
    Calka, Karolina
    Piaskowski, Sylwester
    Urbanska-Rys, Halina
    Salagacka, Aleksandra
    Mirowski, Marek
    Robak, Tadeusz
    LEUKEMIA RESEARCH, 2009, 33 (02) : 332 - 335
  • [2] ABCB1 (MDR1) rs1045642 is associated with increased overall survival in plasma cell myeloma
    Drain, Stephen
    Catherwood, Mark A.
    Orr, Nick
    Galligan, Leeona
    Rea, I. Maeve
    Hodkinson, Clare
    Drake, Mary B.
    Kettle, Paul J.
    Morris, T. C. M. 'Curly'
    Alexander, H. Denis
    LEUKEMIA & LYMPHOMA, 2009, 50 (04) : 566 - 570
  • [3] ABCB1/MDR1 gene polymorphisms as a prognostic factor in colorectal cancer
    Balcerczak, Ewa
    Panczyk, Mariusz
    Piaskowski, Sylwester
    Pasz-Walczak, Grazyna
    Salagacka, Aleksandra
    Mirowski, Marek
    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 2010, 25 (10) : 1167 - 1176
  • [4] Relationship between genetic polymorphisms of drug efflux transporter MDR1 (ABCB1) and response to losartan in hypertension patients
    Goktas, M. T.
    Pepedil, F.
    Karaca, O.
    Kalkisim, S.
    Cevik, L.
    Gumus, E.
    Guven, G. S.
    Babaoglu, M. O.
    Bozkurt, A.
    Yasar, U.
    EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2016, 20 (11) : 2460 - 2467
  • [5] MDR1 variants and risk of Parkinson disease
    Zschiedrich, Katja
    Koenig, Inke R.
    Bruggemann, Norbert
    Kock, Norman
    Kasten, Meike
    Leenders, Klaus L.
    Kostic, Vladimir
    Vieregge, Peter
    Ziegler, Andreas
    Klein, Christine
    Lohmann, Katja
    JOURNAL OF NEUROLOGY, 2009, 256 (01) : 115 - 120
  • [6] Associations Between Variants in the ABCB1 (MDR1) Gene and Corticosteroid Dependence in Children with Crohn's Disease
    Krupoves, Alfreda
    Mack, David
    Seidman, Ernest
    Deslandres, Colette
    Amre, Devendra
    INFLAMMATORY BOWEL DISEASES, 2011, 17 (11) : 2308 - 2317
  • [7] Associations between common variants in the MDR1 (ABCB1) gene and ulcerative colitis among North Indians
    Juyal, Garima
    Midha, Vandana
    Amre, Devendra
    Sood, Ajit
    Seidman, Ernest
    Thelma, B. K.
    PHARMACOGENETICS AND GENOMICS, 2009, 19 (01) : 77 - 85
  • [8] MDR1 (ABCB1) polymorphisms: functional effects and clinical implications
    Leticia Brambila-Tapia, Aniel Jessica
    REVISTA DE INVESTIGACION CLINICA-CLINICAL AND TRANSLATIONAL INVESTIGATION, 2013, 65 (05): : 445 - 454
  • [9] Influence of ABCB1 polymorphisms on the pharmacokinetics and toxicity of lenalidomide in patients with multiple myeloma
    Kobayashi, Takahiro
    Miura, Masatomo
    Abumiya, Maiko
    Akamine, Yumiko
    Ito, Fumiko
    Takahashi, Naoto
    MEDICAL ONCOLOGY, 2019, 36 (06)
  • [10] Multidrug resistance 1 (MDR1/ABCB1) gene polymorphism (rs1045642 C > T) and susceptibility to multiple myeloma: a systematic review and meta-analysis
    Razi, Bahman
    Sarab, Gholamreza Anani
    Omidkhoda, Azadeh
    Alizadeh, Shahab
    HEMATOLOGY, 2018, 23 (08) : 456 - 462