TY - JOUR
T1 - The effects of interleukin 10 and interferon γ cytokine gene polymorphisms on survival after autologous bone marrow transplantation for patients with breast cancer
AU - Wu, Julie M.
AU - Bensen-Kennedy, Debra
AU - Miura, Yuji
AU - Thoburn, Christopher J.
AU - Armstrong, Deborah
AU - Vogelsang, Georgia B.
AU - Hess, Allan D.
N1 - Funding Information:
Supported by grant nos. CA15396 and CA82853 from the National Institutes of Health, and a grant from the Avon Foundation.
PY - 2005/6
Y1 - 2005/6
N2 - Several clinical trials evaluating the induction of autoimmune graft-versus-host disease (GVHD) after autologous bone marrow transplantation (BMT) as antitumor immunotherapy have shown that autologous GVHD is associated with increased production of interleukin (IL)-10. The induction of autologous GVHD also segregated with single nucleotide polymorphisms in the IL-10 promoter region (IL-10-592 and IL-10-1082) and with CA repeats in the first intron of the interferon (IFN)-γ gene. Polymorphisms within these promoter regions can significantly modify the cytokine response because of differential transcription factor efficiency. This study evaluated the relationship between inheritance of polymorphisms within the IL-10 promoter and in the IFN-γ gene and the overall survival of patients who received autologous BMT for metastatic breast cancer. Peripheral mononuclear cells from 87 women enrolled in 3 autologous BMT (plus induction of autologous GVHD) clinical trials were examined. By using a Cox proportional hazard model, trends in survival after autologous BMT were analyzed. The model included inheritance polymorphisms of IL-10-592, IL-10-1082, CA repeats within the first intron of the IFN-γ gene, estrogen and progesterone receptor status, and stage of disease. Increased survival was significantly associated with patients having the IL-10-592 promoter allele associated with high IL-10 production (hazard ratio, 0.23; 95% confidence interval, 0.09-0.55; P = .001). The effect of the strong IL-10 promoter allele on survival seems to be independent of the development of clinical autologous GVHD. However, decreased survival was significantly associated with patients having CA repeats associated with higher IFN-γ transcription (hazard ratio, 2.34; 95% confidence interval, 1.21-4.54; P = .011). Inheritance of specific alleles that modify IL-10 and IFN-γ production may have unexpected effects on the efficacy of immune-based strategies after autologous BMT. Additional studies are necessary to further define the influence of IL-10 and IFN-γ on the immune response after BMT.
AB - Several clinical trials evaluating the induction of autoimmune graft-versus-host disease (GVHD) after autologous bone marrow transplantation (BMT) as antitumor immunotherapy have shown that autologous GVHD is associated with increased production of interleukin (IL)-10. The induction of autologous GVHD also segregated with single nucleotide polymorphisms in the IL-10 promoter region (IL-10-592 and IL-10-1082) and with CA repeats in the first intron of the interferon (IFN)-γ gene. Polymorphisms within these promoter regions can significantly modify the cytokine response because of differential transcription factor efficiency. This study evaluated the relationship between inheritance of polymorphisms within the IL-10 promoter and in the IFN-γ gene and the overall survival of patients who received autologous BMT for metastatic breast cancer. Peripheral mononuclear cells from 87 women enrolled in 3 autologous BMT (plus induction of autologous GVHD) clinical trials were examined. By using a Cox proportional hazard model, trends in survival after autologous BMT were analyzed. The model included inheritance polymorphisms of IL-10-592, IL-10-1082, CA repeats within the first intron of the IFN-γ gene, estrogen and progesterone receptor status, and stage of disease. Increased survival was significantly associated with patients having the IL-10-592 promoter allele associated with high IL-10 production (hazard ratio, 0.23; 95% confidence interval, 0.09-0.55; P = .001). The effect of the strong IL-10 promoter allele on survival seems to be independent of the development of clinical autologous GVHD. However, decreased survival was significantly associated with patients having CA repeats associated with higher IFN-γ transcription (hazard ratio, 2.34; 95% confidence interval, 1.21-4.54; P = .011). Inheritance of specific alleles that modify IL-10 and IFN-γ production may have unexpected effects on the efficacy of immune-based strategies after autologous BMT. Additional studies are necessary to further define the influence of IL-10 and IFN-γ on the immune response after BMT.
KW - Autologous bone marrow transplantation
KW - IFN-γ
KW - IL-10 polymorphisms
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U2 - 10.1016/j.bbmt.2005.03.008
DO - 10.1016/j.bbmt.2005.03.008
M3 - Article
C2 - 15931634
AN - SCOPUS:19944413090
SN - 1083-8791
VL - 11
SP - 455
EP - 464
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 6
ER -