title: Genetic variations in multiple myeloma II: association with effect of treatment.
abstract: 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.
authors: Department of Haematology, Roskilde Hospital, Copenhagen University, Roskilde, Denmark. avag@regionsjaelland.dk
authors: Annette
authors: A
authors: Vangsted
authors: Tobias W
authors: TW
authors: Klausen
authors: Ulla
authors: U
authors: Vogel
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D058978:Reduced Folate Carrier Protein / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase