title: Polymorphism of IL-10 receptor β affects the prognosis of multiple myeloma patients treated with thalidomide and/or bortezomib.
abstract: Interleukin-10 (IL-10) and IL-10 receptor (IL-10R) single nucleotide polymorphisms have been implicated in the pathogenesis of many cancers. We investigated the influence of IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E on the risk of developing multiple myeloma (MM) and the clinical features of MM. We extracted the genomic DNA from 128 MM patients and 202 healthy controls and used polymerase chain reaction-restriction fragment length polymorphism method to detect IL-10 promoter -592C/A (rs1800872), IL-10RA (rs2228055), and IL-10RB K47E (rs2834167) genotypes. Overall survival (OS) was defined as the interval from the date of diagnosis to the date of death or last clinical appointment. No statistically significant difference was observed in the genotype and allele frequencies of IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E between MM patients and healthy controls. IL-10RA II genotype was significantly associated with a hemoglobin level lower than that of IV and VV genotypes (mean ± standard deviation, 9.21 ± 2.46 vs 10.3 ± 2.33 g/dL; P = .021). IL-10 -592 AA genotype was significantly associated with OS better than that of CA and CC genotypes (median OS, 74.5 vs 46.3 months; P = .047). We observed significant differences in survival between patients treated with thalidomide and/or bortezomib and those treated with conventional treatments (median OS, 74.5 vs 38.2 months; P = .021). Therefore, we also examined the effect of IL-10 and IL-10R polymorphisms on the clinical variables and OS of patients treated with thalidomide and/or bortezomib. In addition, IL-10RB EE genotype was significantly associated with poorer survival than KK and KE genotypes (median OS, 46.3 vs 78.8 months; P = .015). Our findings indicate that IL-10 and IL-10R gene polymorphisms may not contribute to the susceptibility to MM but may be associated with the severity and prognosis of MM. In particular, IL-10RB K47E polymorphism may contribute to the poor prognosis of MM patients treated with thalidomide and/or bortezomib.
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kasamatsu
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Saitoh
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Ino
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: Nanami
authors.initials: N
authors.lastname: Gotoh
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Takeki
authors.initials: T
authors.lastname: Mitsui
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: National Hospital Organization, Nishigunma National Hospital, Shibukawa, Gunma, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: National Hospital Organization, Nishigunma National Hospital, Shibukawa, Gunma, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Sawamura
authors.affiliation: Blood Transfusion Service, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yokohama
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.affiliation: Oncology Center, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Tsukamoto
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Murakami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069286:Bortezomib / Q000008:administration & dosage / Q000627:therapeutic use; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D053710:Interleukin-10 Receptor beta Subunit; D016753:Interleukin-10; D013792:Thalidomide; D000069286:Bortezomib
keywords: bortezomib; interleukin-10 receptor; multiple myeloma; polymorphism; thalidomide