The Effects of Interleukin 10 and Interferon γ Cytokine Gene Polymorphisms on Survival after Autologous Bone Marrow Transplantation for Patients with Breast Cancer

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.