Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma.
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.
Division of Epidemiology, College of Public Health, Ohio State University, Columbus, Ohio, United States of America; Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
Judith
J
Schwartzbaum
Division of Biostatistics, College of Public Health, Ohio State University, Columbus, Ohio, United States of America; Mathematical Biosciences Institute, Columbus, Ohio, United States of America; Department of Mathematics, University of Lodz, Lodz, Poland.
Michal
M
Seweryn
Department of Statistics, Ohio State University, Columbus, Ohio, United States of America.
Christopher
C
Holloman
Division of Epidemiology, College of Public Health, Ohio State University, Columbus, Ohio, United States of America; Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.
Randall
R
Harris
Center for Pharmacogenetics, Wexner Medical Center, Ohio State University, Columbus, Ohio, United States of America.
Samuel K
SK
Handelman
Division of Biostatistics, College of Public Health, Ohio State University, Columbus, Ohio, United States of America; Mathematical Biosciences Institute, Columbus, Ohio, United States of America.
Grzegorz A
GA
Rempala
RayBiotech, Inc., Norcross, Georgia, United States of America; RayBiotech, Inc. Guangzhou, China.
Ruo-Pan
RP
Huang
RayBiotech, Inc., Norcross, Georgia, United States of America.
Brett
B
Burkholder
Buckeye Psychiatry, Columbus, Ohio, United States of America.
Adam
A
Brandemihl
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Henrik
H
Kallberg
Department of Registration, Cancer Registry of Norway, Oslo, Norway.
Tom Borge
TB
Johannesen
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Anders
A
Ahlbom
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Maria
M
Feychting
Department of Research, Cancer Registry of Norway, Oslo, Norway.
Tom K
TK
Grimsrud
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000097:blood* / Q000150:complications / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D005910:Glioma / Q000097:blood* / Q000150:complications / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000097:blood* / Q000150:complications / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009664:Norway; D012042:Registries; D012307:Risk Factors
D016207:Cytokines