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POLYMORPHISM OF IL-10 RECEPTOR ? AFFECTS THE PROGNOSIS OF MULTIPLE MYELOMA PATIENTS TREATED WITH THALIDOMIDE AND/OR BORTEZOMIB
Author(s): ,
Tetsuhiro Kasamatsu
Affiliations:
Graduate School of Health Sciences,Gunma University,Maebashi, Gunma,Japan
,
Takayuki Saitoh
Affiliations:
Graduate School of Health Sciences,Gunma University,Maebashi, Gunma,Japan
,
Rumi Ino
Affiliations:
Graduate School of Health Sciences,Gunma University,Maebashi, Gunma,Japan
,
Yuya Kitamura
Affiliations:
Graduate School of Health Sciences,Gunma University,Maebashi, Gunma,Japan
,
Kazuki Honma
Affiliations:
Graduate School of Health Sciences,Gunma University,Maebashi, Gunma,Japan
,
Nanami Gotoh
Affiliations:
Graduate School of Health Sciences,Gunma University,Maebashi, Gunma,Japan
,
Hiroshi Handa
Affiliations:
Department of Medicine and Clinical Science,Gunma University,Maebashi, Gunma,Japan
,
Morio Matsumoto
Affiliations:
Nishigunma National Hospital,Shibukawa, Gunma,Japan
,
Morio Sawamura
Affiliations:
Nishigunma National Hospital,Shibukawa, Gunma,Japan
,
Akihiko Yokohama
Affiliations:
Blood Transfusion Service,Gunma University Hospital,Maebashi, Gunma,Japan
,
Norifumi Tsukamoto
Affiliations:
Oncology Center,Gunma University Hospital,Maebashi, Gunma,Japan
Hirokazu Murakami
Affiliations:
Graduate School of Health Sciences,Gunma University,Maebashi, Gunma,Japan
(Abstract release date: 05/19/16) EHA Library. Kasamatsu T. 06/09/16; 134839; PB1939
Mr. Tetsuhiro Kasamatsu
Mr. Tetsuhiro Kasamatsu
Contributions
Abstract
Abstract: PB1939

Type: Publication Only

Background
Interleukin-10 (IL-10) and IL-10 receptor (IL-10R) single nucleotide polymorphisms (SNPs) have been implicated in the pathogenesis of many cancers, including hematologic malignancy. However, no previous studies have examined the possible association between IL-10/IL-10R SNPs and MM, especially prognosis in MM patients. 

Aims
We investigated the influence of IL-10 -592C/A, IL-10RA I224V and IL-10RB K47E on the risk to develop multiple myeloma (MM) and clinical features of MM.

Methods
We extracted the genomic DNA from 128 MM patients and 202 healthy controls, and determined IL-10 promoter-592C/A (rs1800872), IL-10RA (rs2228055) and IL-10RB K47E (rs2834167) genotypes by using the PCR-restriction fragment length polymorphism method. Overall survival (OS) was defined as the interval from the date of diagnosis to the date of death or last clinical appointment.

Results
No statistically significant differences were observed in the genotype and allele frequencies of IL-10 -592C/A, IL-10RA I224V and IL-10RB K47E between MM patients and healthy control. IL-10RA II genotype was significantly associated with lower hemoglobin level than IV and VV genotypes (mean ± standard deviation, 9.21 ± 2.46 vs. 10.3 ± 2.33 g/dl, P = 0.021). IL-10 -592 AA genotype was significantly associated with better OS than CA and CC genotypes (median OS, 74.5 vs. 46.3 months, P = 0.047). We observed significant differences in survival between patients treated with thalidomide and/or bortezomib and with conventional treatment (median OS, 74.5 vs. 38.2 months, P = 0.021). Therefore, we also examined the effect of IL-10 and IL-10R polymorphisms on clinical variables and OS in patients treated with thalidomide and/or bortezomib. IL-10-592 AA genotype was significantly associated with low albumin level than CA and CC genotypes (mean ± standard deviation, 9.21 ± 2.46 vs. 10.3 ± 2 .33 g/dl, P = 0.021). In addition, IL-10RB EE genotype was significantly associated with poor survival than KK and KE genotypes (median OS, 46.3 vs. 78.8 months, P = 0.015) (Figure 1). 

Conclusion
Our findings indicate that IL-10 and IL-10R gene polymorphisms may not contribute to susceptibility to MM, but they may be associated with the severity and prognosis of MM. Especially, IL-10RB K47E polymorphism influence the poor prognosis of patients treated with thalidomide and/or bortezomib.



Session topic: E-poster

Keyword(s): Bortezomib, IL-10, Polymorphism, Thalidomide
Abstract: PB1939

Type: Publication Only

Background
Interleukin-10 (IL-10) and IL-10 receptor (IL-10R) single nucleotide polymorphisms (SNPs) have been implicated in the pathogenesis of many cancers, including hematologic malignancy. However, no previous studies have examined the possible association between IL-10/IL-10R SNPs and MM, especially prognosis in MM patients. 

Aims
We investigated the influence of IL-10 -592C/A, IL-10RA I224V and IL-10RB K47E on the risk to develop multiple myeloma (MM) and clinical features of MM.

Methods
We extracted the genomic DNA from 128 MM patients and 202 healthy controls, and determined IL-10 promoter-592C/A (rs1800872), IL-10RA (rs2228055) and IL-10RB K47E (rs2834167) genotypes by using the PCR-restriction fragment length polymorphism method. Overall survival (OS) was defined as the interval from the date of diagnosis to the date of death or last clinical appointment.

Results
No statistically significant differences were observed in the genotype and allele frequencies of IL-10 -592C/A, IL-10RA I224V and IL-10RB K47E between MM patients and healthy control. IL-10RA II genotype was significantly associated with lower hemoglobin level than IV and VV genotypes (mean ± standard deviation, 9.21 ± 2.46 vs. 10.3 ± 2.33 g/dl, P = 0.021). IL-10 -592 AA genotype was significantly associated with better OS than CA and CC genotypes (median OS, 74.5 vs. 46.3 months, P = 0.047). We observed significant differences in survival between patients treated with thalidomide and/or bortezomib and with conventional treatment (median OS, 74.5 vs. 38.2 months, P = 0.021). Therefore, we also examined the effect of IL-10 and IL-10R polymorphisms on clinical variables and OS in patients treated with thalidomide and/or bortezomib. IL-10-592 AA genotype was significantly associated with low albumin level than CA and CC genotypes (mean ± standard deviation, 9.21 ± 2.46 vs. 10.3 ± 2 .33 g/dl, P = 0.021). In addition, IL-10RB EE genotype was significantly associated with poor survival than KK and KE genotypes (median OS, 46.3 vs. 78.8 months, P = 0.015) (Figure 1). 

Conclusion
Our findings indicate that IL-10 and IL-10R gene polymorphisms may not contribute to susceptibility to MM, but they may be associated with the severity and prognosis of MM. Especially, IL-10RB K47E polymorphism influence the poor prognosis of patients treated with thalidomide and/or bortezomib.



Session topic: E-poster

Keyword(s): Bortezomib, IL-10, Polymorphism, Thalidomide

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