Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma
PLOS ONE
Authors: Schwartzbaum, Judith; Seweryn, Michal; Holloman, Christopher; Harris, Randall; Handelman, Samuel K.; Rempala, Grzegorz A.; Huang, Ruo-Pan; Burkholder, Brett; Brandemihl, Adam; Kallberg, Henrik; Johannesen, Tom Borge; Ahlbom, Anders; Feychting, Maria; Grimsrud, Tom K.
Abstract
Allergy is inversely related to glioma risk. To determine whether prediagnostic allergy-related serum proteins are associated with glioma, we conducted a nested case-control study of seven cytokines (IL4, IL13, IL5, IL6, IL10, IFNG, TGFB2), two soluble cytokine receptors (sIL4RA, sIL13RA2) and three allergy-related transcription factors (FOXP3, STAT3, STAT6) using serum specimens from the Janus Serum Bank Cohort in Oslo, Norway. Blood donors subsequently diagnosed with glioma (n = 487) were matched to controls (n = 487) on age and date of blood draw and sex. We first estimated individual effects of the 12 serum proteins and then interactions between IL4 and IL13 and their receptors using conditional logistic regression. We next tested equality of case-control inter-correlations among the 12 serum proteins. We found that TGFB2 is inversely related to glioblastoma (Odds Ratio (OR) = 0.87, 95% Confidence Interval (CI)) = 0.76, 0.98). In addition, <= 5 years before diagnosis, we observed associations between IL4 (OR = 0.82, 95% CI = 0.66, 1.01), sIL4RA (OR = 0.80, 95% CI = 0.65, 1.00), their interaction (OR = 1.06, 95% CI = 1.01, 1.12) and glioblastoma. This interaction was apparent > 20 years before diagnosis (IL4-sIL4RA OR = 1.20, 95% CI = 1.05, 1.37). Findings for glioma were similar. Case correlations were different from control correlations stratified on time before diagnosis. Five years or less before diagnosis, correlations among case serum proteins were weaker than were those among controls. Our findings suggest that IL4 and sIL4RA reduce glioma risk long before diagnosis and early gliomagenesis affects circulating immune function proteins.
Cyst Fluid Interleukin-1 beta (IL1 beta) Levels Predict the Risk of Carcinoma in Intraductal Papillary Mucinous Neoplasms of the Pancreas
CLINICAL CANCER RESEARCH
Authors: Maker, Ajay V.; Katabi, Nora; Qin, Li-Xuan; Klimstra, David S.; Schattner, Mark; Brennan, Murray F.; Jarnagin, William R.; Allen, Peter J.
Abstract
Purpose: Biomarkers for high-grade dysplasia in patients with radiographically identified intraductal papillary mucinous neoplasms (IPMN) have not been described. We hypothesized that dysplasia in IPMN invokes an immunogenic/proinflammatory microenvironment that can be identified by cyst fluid cytokine levels. Experimental Design: Pancreatic cyst fluid aspirates were collected at resection (2005-2009). Samples were grouped into low-risk [low-grade (n = 6) or moderate dysplasia (n = 15)] and high-risk groups [high-grade dysplasia (n = 13) or carcinoma (n = 6)]. Cytokine expression was determined using a multiplex sandwich immunoassay. Differences in cytokine expression were evaluated using the 2-sample t test. Sample classification was performed using a logistic regression adjusting for sample covariates. Results: IL5 and IL8 concentrations were higher in the cyst fluid from patients in the high-risk group than the low-risk group. Interleukin (IL)-1 beta concentrations were also higher in the cyst fluid from patients with high-grade dysplasia or cancer (n = 19) than those with low-or moderate-grade dysplasia (n = 21, 539 +/- 255 pg/mL vs. 0.2 +/- 0.1 pg/mL; P < 0.0001). IL1 beta remained a significant predictor of high-risk cysts after multivariate analysis. There was no significant difference in levels of IL2, IL4, IL10, IL12, IL13, TNF-alpha, or IFN-gamma between the groups. That IL1 beta levels identified cysts at a high risk of malignancy was confirmed in an independent validation set. Conclusions: Cyst fluid levels of IL1 beta can differentiate low-from high-risk IPMN. This study introduces IL1 beta as a potential biomarker for validation in larger clinical studies. Clin Cancer Res; 17(6); 1502-8. (C) 2011 AACR.