The Relationship of ABCB1/MDR1 and CYP1A1 Variants with the Risk of Disease Development and Shortening of Overall Survival in Patients with Multiple Myeloma
(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.
机构:
Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Univ Montreal, Dept Prevent & Social Med, Montreal, PQ, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Krupoves, Alfreda
Seidman, Ernest G.
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McGill Univ, Ctr Hlth, Dept Med, Div Gastroenterol, Montreal, PQ, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Seidman, Ernest G.
Mack, David
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Childrens Hosp Eastern Ontario, Div Gastroenterol Hepatol & Nutr, Ottawa, ON K1H 8L1, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Mack, David
Israel, David
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British Columbia Childrens Hosp, Div Gastroenterol & Nutr, Vancouver, BC V6H 3V4, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Israel, David
Morgan, Kenneth
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McGill Univ, Ctr Hlth, Res Inst, Dept Human Genet & Med, Montreal, PQ, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Morgan, Kenneth
Lambrette, Philippe
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Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Lambrette, Philippe
Costea, Irina
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Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Univ Montreal, Dept Prevent & Social Med, Montreal, PQ, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Costea, Irina
Deslandres, Colette
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Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Deslandres, Colette
Grimard, Guy
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Hop St Justine, Div Orthopaed, Montreal, PQ H3T 1C5, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Grimard, Guy
Law, Liliane
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Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Law, Liliane
Levy, Emile
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Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Levy, Emile
Amre, Devendra K.
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Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
Univ Montreal, Dept Paediat, Montreal, PQ, CanadaHop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada
机构:
Univ Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, Brazil
de Oliveira, Juliana
Felipe, Aledson Vitor
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Univ Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, Brazil
Felipe, Aledson Vitor
Artigiani Neto, Ricardo
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Univ Fed Sao Paulo, UNIFESP, Dept Pathol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, Brazil
Artigiani Neto, Ricardo
Oshima, Celina Tizuko
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Univ Fed Sao Paulo, UNIFESP, Dept Pathol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, Brazil
Oshima, Celina Tizuko
Silva, Marcelo de Souza
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Univ Fed Sao Paulo, UNIFESP, Dept Pathol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, Brazil
Silva, Marcelo de Souza
Forones, Nora Manoukian
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Univ Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Div Gastroenterol, Dept Med, UNIFESP, Sao Paulo, SP, Brazil
机构:
Cumhuriyet Univ, Dept Med Genet, Fac Med, Sivas, TurkeyCanakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey
Ozen, Filiz
Silan, Coskun
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Canakkale Onsekiz Mart Univ, Dept Pharmacol, Fac Med, TR-17100 Canakkale, TurkeyCanakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey
Silan, Coskun
Uludag, Ahmet
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Canakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, TurkeyCanakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey
Uludag, Ahmet
Candan, Ferhan
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Cumhuriyet Univ, Dept Internal Med, Fac Med, Sivas, TurkeyCanakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey
Candan, Ferhan
Silan, Fatma
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Canakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, TurkeyCanakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey
Silan, Fatma
Ozdemir, Semra
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Cumhuriyet Univ, Dept Nucl Med, Fac Med, Sivas, TurkeyCanakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey
Ozdemir, Semra
Atik, Sinem
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Canakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, TurkeyCanakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey
Atik, Sinem
Ozdemir, Ozturk
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Canakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey
Cumhuriyet Univ, Dept Med Genet, Fac Med, Sivas, TurkeyCanakkale Onsekiz Mart Univ, Dept Med Genet, Fac Med, TR-17100 Canakkale, Turkey