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

International Journal of Cancer - Tập 135 Số 4 - Trang 913-922 - 2014
Kerstin L. Edlefsen1,2, Otoniel Martı́nez-Maza3,4,5,6, Margaret M. Madeleine7,8, Larry Magpantay4,5,6, Dana K. Mirick8, Kenneth J. Kopecky8, Andrea Z. LaCroix7,9,8, Anneclaire J. De Roos10,8
1Conflicts of interest: The authors have no conflicts of interest to report.
2Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA
3Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA
4Departments of Obstetrics & Gynecology, and Microbiology, Immunology & Molecular Genetics David Geffen School of Medicine at UCLA Los Angeles CA
5Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA
6UCLA AIDS Institute, University of California, Los Angeles, CA
7Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA
8Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA
9Department of Family and Preventive Medicine, University of California, San Diego, CA
10Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, PA

Tóm tắt

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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International Journal of Cancer

Tập 135 Số 4

913-922

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