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Genetic variations in multiple myeloma II: association with effect of treatment

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  1. Unexpected, isolated activated partial thromboplastin time prolongation: A practical mini-review

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  2. Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes

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  3. Addressing the room for improvement in management of acute promyelocytic leukemia

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Association studies on genetic variation to treatment effect may serve as a predictive marker for effect of treatment and can also uncover biological pathways behind drug effect. Single-nucleotide polymorphisms (SNPs) have been studied in relation to high-dose treatment (HDT), thalidomide- and bortezomib-based therapy, maintenance treatment with interferon-α and in relation to therapy-related adverse effects caused by treatment. Candidate genes for prediction of effect of HDT include DNA repair genes, CYP genes and genes involved in inflammation and apoptosis such as IL1B and RAI. In thalidomide- and bortezomid-based therapy, candidate genes include TNFA and genes involved in the nuclear factor kappa B pathway (NFKB2 and TRAF3), respectively. In maintenance treatment with interferon-α, a polymorphism in gene NFKB1 is a candidate gene for prediction for effect. Adverse effect includes infection, osteonecrosis of the jaw (ONJ), venous thrombotic events (VTE) and peripheral neuropathy (PN). A SNP in MBL2 and MPO gene was associated with septicemia and a SNP in the gene CYP2C8 was strongly associated with ONJ. Several SNPs in genes encoding DNA repair, apoptosis, inflammation and genes involved in function of the nervous system have been associated with VTE induced by thalidomide and with PN induced by bortezomib. SNP analysis is simple and can be performed, e.g., on blood and buccal cells. Further analysis of SNPs in clinical trials is needed, and collaboration between scientific groups will be an advantage because SNP analysis required large number of patients.
Original languageEnglish
JournalEuropean Journal of Haematology
Volume88
Issue number2
Pages (from-to)93-117
Number of pages25
ISSN0902-4441
DOIs
Publication statusPublished - 2012

    Research areas

  • Antineoplastic Combined Chemotherapy Protocols, Cytochrome P-450 Enzyme System, DNA Repair, Gene Expression Regulation, Neoplastic, Glutathione Transferase, Humans, Inflammation, Multiple Myeloma, P-Glycoprotein, Polymorphism, Single Nucleotide, Reduced Folate Carrier Protein, Treatment Outcome

ID: 34758274