| BackgroundCancer was a type of general and systemic disease. Futhermore, human immune system play crucial role in the formation of cancer. As such, therapeutic strategy for cancer has changed from elimination of tumor burden into remodeling and retaining of patients'immune function. The relationship between human immune system and cancer etiology, and explore novel treatment have become an emerging research area in recent years.PurposeTo inverstigate the relationship between immune system and cancer etiology, and explore novel treatment for cancer, we performed three studies as following:Study 1:Early effects of low dose 12C6+ ion or X-ray irradiation on human peripheral blood lymphocytes;Study 2:Early effects of low dose 12C6+ ion or X-ray irradiation on peripheral blood lymphocytes of patients with alimentary cancer;Study 3:Cytokine Polymorphisms in Thl/Th2 Pathway, Body Mass Index, and Risk of Non-Hodgkin Lymphoma.Methods & ResultsStudy 11) Cell level (Percentages of T and NK cells subsets were detected by flow cytometry):There was no significant change in the percentage of T and NK cells subsets of peripheral blood lymphocyte (PBL) at 24h after low dose 12C6+ ion or X-ray irradiation. 2) mRNA and protein levels (mRNA expression of interleukin-2, tumor necrosis factor-αand interferon-γwere examined by real time quantitative RT-PCR; cytokines proetein productions were examined by enzyme-linked immunosorbent assays):mRNA expression of IL-2, IFN-y and TNF-a in PBL and their protein levels in supernatant were significantly increased at 24 h after exposure to 0.05 Gy 12C6+ ions radiation and the effects were stronger than observed for X-ray exposure.3) Effect level (cytotoxic activities of PBL were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide):The cytotoxic activity of PBL was significantly increased at 24 h after exposure to 0.05 Gy 12C6+ ions radiation and the effects were more significant than observed for X-ray exposure.Study 21) Cell level:The percentage of T lymphocyte subsets was significantly increased 24 hours after exposure to low dose radiation. And the effect was more pronounced in the group receiving 0.05Gy 12C6+ ion irradiation than the group receiving X-ray irradiation. However, there was no significant change in the percentage of NK cell subsets.2) mRNA and protein levels:mRNA expression levels of IL-2 and IFN-y in PBL, and their protein levels in supernatant were significantly increased 24 hours after exposure to low dose radiation. The effects were more pronounced in the group receiving 0.05Gy 12C6+ ion irradiation than the group receiving X-ray irradiation. However, there was no significant change in the TNF-a production of PBL.Study 31) Study population:Finally, a total of 1115 subjects were selected for our study,including 518 cases, and 597 controls;2) Data collection:In-person interview demographic characteristics, usual adult height and weight, diet;3) Genotyping was performed using ABI 7900HT detection system with 100% concordance with sequence analysis of 102 individuals as listed on the SNP500Cancer website. A total of 39 SNPs in 20 Thl/Th2 immune genes were selected for genotyping.4) Unconditional logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for associations between BMI, and risk of NHL and its subtypes in different genotype strata. Compared to women with normal weight, those with a BMI≥25.0 had an increased risk of NHL overall, B-cell lymphoma and T-cell lymphoma.5) Significance of gene-BMI interaction was assessed by adding an interaction term in the logistic models. The False Discovery Rate (FDR) method set at 0.2 was used to control for multiple comparisons. All P values presented are 2-sided and all analyses were performed using SAS Software, version 9.2 (SAS Institute, Cary, NC):The genetic variations in IFNGR2 (rs9808753), IL5 (rs2069812), IL7R (rs1494555), TNF (rs1799724), IL5 (rs2069812), IL13(rs20541), and IL12A(rs568408) significantly modify the relationship between BMI and risk of NHL overall and subtypes.Discussion:Study 1:Our study provides the first evidence that exposure to 0.05 Gy 12C6+ ions radiation induce immunopotentiation. And the effect was more pronounced compared to X-ray. As such, we therefore hypothesized that apply low dose heavy ions irradiation into cancer patients.Study 2:Our study provides the first evidence that exposure to 0.05Gy 12C6+ion irradiation could alleviate the immune suppression in alimentary tract cancer patients. Low dose 12C6+ ions could therefore be considered a potential novel form of immunotherapy, with greater efficiency than conventional LDI using low LET radiation, such as X-ray.Study 3:In summary, our study suggests that common genetic variations in the Th1/Th2 pathways genes may modify the association between BMI and risk of NHL. |
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