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Cytokines in serum in relation to future non-Hodgkin lymphoma risk: evidence for associations by histologic subtype
Journal article   Peer reviewed

Cytokines in serum in relation to future non-Hodgkin lymphoma risk: evidence for associations by histologic subtype

Kerstin L Edlefsen, Otoniel Martínez-Maza, Margaret M Madeleine, Larry Magpantay, Dana K Mirick, Kenneth J Kopecky, Andrea Z LaCroix and Anneclaire J De Roos
International journal of cancer, v 135(4), pp 913-922
15 Aug 2014
PMID: 24488825

Abstract

Aged Alleles Biomarkers, Tumor - blood Case-Control Studies Cytokines - blood Female Gene Expression Regulation, Neoplastic Humans Immune System Inflammation Interleukin-10 - blood Lymphoma, B-Cell - blood Lymphoma, B-Cell - diagnosis Lymphoma, Non-Hodgkin - blood Lymphoma, Non-Hodgkin - diagnosis Middle Aged Multivariate Analysis Polymorphism, Genetic Postmenopause Risk Factors Tumor Necrosis Factor-alpha - blood
Specific associations for lymphoma in the general population suggest that chronic immune dysfunction/dysregulation may be associated with the development of B-cell non-Hodgkin lymphoma (NHL). Furthermore, polymorphisms in several cytokine genes have been associated with increased lymphoma risk, most consistently with genes for TNF and IL10. To evaluate the hypothesis that prediagnostic circulating cytokine levels would be associated with increased B-cell lymphoma risk, we conducted a nested case-control study within the Women's Health Initiative Observational Study cohort involving 491 B-cell NHL cases and 491 controls. Levels of eleven cytokines, including IL1β, IL2, IL4, IL5, IL6, IL10, IL12, IL13, TNF, IFNγ and GM-CSF, were measured using a Luminex suspension bead-based multiplexed array in prediagnostic serum samples collected a median of 6 years prior to the lymphoma diagnosis. We observed a modestly increased risk of all B-cell NHL in women with increased levels of the cytokines TNF and IL10 (OR1.22, CI 1.07-1.38 and OR 1.09, CI 1.04-1.15, respectively, per doubling in the serum cytokine concentration) and this association showed some variation according to histologic subtype. The increased risk was strongest for those neoplasms diagnosed in close proximity to the blood draw for some histologic subtypes but not others, suggesting a component of reverse causation. Further study will be required to better understand how genetic polymorphisms in TNF and IL10 genes may interact with circulating cytokine levels and states of chronic immune dysfunction/stimulation to contribute to the risk of B-cell NHL.

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Collaboration types
Domestic collaboration
Web of Science research areas
Oncology
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