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.
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Belfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Drain, Stephen
Catherwood, Mark A.
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Belfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Catherwood, Mark A.
Orr, Nick
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Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JP, EnglandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Orr, Nick
Galligan, Leeona
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Belfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Galligan, Leeona
Rea, I. Maeve
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Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast BT9 7BL, Antrim, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Rea, I. Maeve
Hodkinson, Clare
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Belfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Hodkinson, Clare
Drake, Mary B.
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Belfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Drake, Mary B.
Kettle, Paul J.
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Belfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Kettle, Paul J.
Morris, T. C. M. 'Curly'
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Belfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Morris, T. C. M. 'Curly'
Alexander, H. Denis
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Belfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North IrelandBelfast City Hosp, Belfast HSC Trust, Dept Haematol, Haematooncol Lab, C Floor, Belfast BT9 7AB, Antrim, North Ireland
机构:
Univ Delhi, Dept Genet, New Delhi 110021, IndiaHop St Justine, Res Ctr, Bur A 728, Montreal, PQ H3T 1C5, Canada
Juyal, Garima
Midha, Vandana
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Dayanand Med Coll & Hosp, Ludhiana, Punjab, IndiaHop St Justine, Res Ctr, Bur A 728, Montreal, PQ H3T 1C5, Canada
Midha, Vandana
Amre, Devendra
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Hop St Justine, Res Ctr, Bur A 728, Montreal, PQ H3T 1C5, Canada
Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, CanadaHop St Justine, Res Ctr, Bur A 728, Montreal, PQ H3T 1C5, Canada
Amre, Devendra
Sood, Ajit
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Dayanand Med Coll & Hosp, Ludhiana, Punjab, IndiaHop St Justine, Res Ctr, Bur A 728, Montreal, PQ H3T 1C5, Canada
Sood, Ajit
Seidman, Ernest
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McGill Univ, Dept Med, Ctr Hlth, Montreal, PQ, CanadaHop St Justine, Res Ctr, Bur A 728, Montreal, PQ H3T 1C5, Canada
Seidman, Ernest
Thelma, B. K.
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Univ Delhi, Dept Genet, New Delhi 110021, IndiaHop St Justine, Res Ctr, Bur A 728, Montreal, PQ H3T 1C5, Canada