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

• Published in: International journal of cancer Vol. 135; no. 4; pp. 913 - 922
• Main Authors: Edlefsen, Kerstin L., Martínez‐Maza, Otoniel, Madeleine, Margaret M., Magpantay, Larry, Mirick, Dana K., Kopecky, Kenneth J., LaCroix, Andrea Z., Roos, Anneclaire J.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 15.08.2014; Wiley Subscription Services, Inc
• Subjects: Aged; Alleles; Biological and medical sciences; Biomarkers, Tumor - blood; Cancer; Case-Control Studies; cohort studies; Cytokines; Cytokines - blood; epidemiology; Female; Gene Expression Regulation, Neoplastic; Genotype & phenotype; Hematologic and hematopoietic diseases; Histology; Humans; Immune System; Inflammation; Interleukin-10 - blood; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma; Lymphoma, B-Cell - blood; Lymphoma, B-Cell - diagnosis; Lymphoma, Non-Hodgkin - blood; Lymphoma, Non-Hodgkin - diagnosis; Medical research; Medical sciences; Middle Aged; Multivariate Analysis; non‐Hodgkin lymphoma; Polymorphism, Genetic; Postmenopause; Risk Factors; Tumor Necrosis Factor-alpha - blood; Tumors; Womens health; Cytokine; Risk; Malignant hemopathy; non-Hodgkin lymphoma; Non Hodgkin lymphoma; Epidemiology; Anatomic pathology; Association; Cancerology; Histopathology; Lymphoproliferative syndrome; Cohort study; Risk factor; Histological type; cohort studies; Serum; cytokines; Cancer; epidemiology
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28724

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. What's new? Chronic immune dysregulation is associated with the development of certain subtypes of B‐cell non‐Hodgkin lymphoma (NHL). However, the relationship between B‐cell NHL and immune function is complex. Here, in a study of B‐cell NHL cases within the Women's Health Initiative Observational Study cohort, increased pre‐diagnostic serum concentrations of the cytokines TNF and IL10 were found to be associated with an increased risk of future B‐cell NHL. Polymorphisms in TNF and IL10 previously have been associated with an increased risk of lymphoma. Further investigation is needed to understand how genotype and phenotype interact to contribute to lymphoma risk.