Plasma Cytokines and Future Risk of Non-Hodgkin Lymphoma (NHL): A Case-Control Study Nested in the Italian European Prospective Investigation into Cancer and Nutrition

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BlankPlasma Cytokines and Future Risk of Non-Hodgkin Lymphoma (NHL): A

Case-Control Study Nested in the Italian European Prospective Investigation into

Cancer and Nutrition.

1.. Fatemeh Saberi Hosnijeh1,3,

2.. Esmeralda J.M. Krop1,

3.. Chiara Scoccianti4,10,

4.. Vittorio Krogh5,

5.. Domenico Palli6,

6.. Salvatore Panico7,

7.. rio Tumino8,

8.. Carlotta Sacredote9,

9.. Niga Nawroly10,

10.. Lützen Portengen1,

11.. Jakob Linseisen11,

12.. Paolo Vineis10 and

13.. Roel Vermeulen1,2

+ Author Affiliations

1.. Authors' Affiliations:1Institute for Risk Assessment Sciences, Division of

Environmental Epidemiology, Utrecht University; 2Julius Center for Health

Sciences and Primary Care, University Medical Center Utrecht, Utrecht,

Netherlands; 3Zanjan University of Medical Science, Zanjan, Iran; 4IARC, Lyon,

France; 5Nutritional Epidemiology Unit, National Cancer Institute, Milan, Italy;

6Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention

Centre, Scientific Institute of Tuscany, Florence, Italy; 7Department of

Clinical and Experimental Medicine, Federico II University of Naples, Napoli,

Italy; 8Ragusa Cancer Registry, Ragusa, Italy; 9Institute for Scientific

Interchange Foundation, Torino, Italy; 10Imperial College, London, United

Kingdom; and 11Institute of Epidemiology, Helmholtz Zentrum München, München,

Germany

1.. Corresponding Author:

Roel Vermeulen, Institute for Risk Assessment Sciences, Division of

Environmental Epidemiology, Utrecht University, Jenalaan 18D, 3584 CK Utrecht,

the Netherlands. Phone: 31-30-253-9448; Fax: 31-30-253-9499. E-mail:

R.C.H.Vermeulen@...

Abstract

Background: Recently, biological markers related to the immune system such as

cytokines have been studied to further understand the etiology of non-Hodgkin

Lymphoma (NHL). However, to date, there are no studies that have studied

cytokine levels prospectively in relation to NHL risk in the general population.

Methods: Using bead-based immunoassays, plasma levels of 11 cytokines, 4

chemokines, and 1 adhesion molecules were measured in prediagnostic blood

samples of 86 NHL cases and 86 matched controls (average time between blood

collection and diagnosis, 4.5 y). Conditional logistic regression adjusted for

body mass index and alcohol consumption was used to analyze the association

between individual plasma cytokine levels and the risk of developing NHL.

Results: In multivariate models, excluding cases diagnosed within 2 years after

inclusion, we observed a significant association for interleukin 2 (IL2; P trend

= 0.004), interferon (IFN)-? (P trend = 0.05), and intercellular adhesion

molecule (ICAM) (P trend = 0.04). Subanalyses of B-cell NHL patients showed a

significant association with IL2 (P trend = 0.003), tumor necrosis factor-a

(TNF-a; P trend = 0.03), and ICAM (P trend = 0.04) and a borderline association

with IL5 (P trend = 0.07) and IFN-? (P trend = 0.08).

Conclusions: The results of this study suggest, in a prospective setting, a

possible association between plasma levels of IL2, ICAM, IFN-?, and TNF-a with

NHL risk and provide some evidence that risk of NHL might be related to a

downregulation of T helper 1 cytokines.

Impact: Identification of subtle changes in immune response regulation

quantified by plasma cytokine levels possibly provides new insights in the

etiology of NHL. Cancer Epidemiol Biomarkers Prev; 19(6); 1577–84. ©2010 AACR.