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Soluble B-cell activation marker of sCD27 and sCD30 and future risk of B-cell lymphomas: a nested case-control study and meta-analyses
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
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2016 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 10, p. 2357-2367Article in journal (Refereed) Published
Abstract [en]

Pre-diagnostic serum/plasma concentrations of B-cell activation markers have been associated with future risk of B-cell lymphomas (BCL) in HIV-infected patients and in the general population. Current evidence for the general population is however limited and relies on relatively small numbers of observations, especially for specific histologies. We carried out a nested case-control study, including 218 BCL and 218 matched controls, within two prospective cohorts, to investigate the association between plasma levels of soluble (s)CD27 and sCD30 and future risk of BCL, and main histologic subtypes separately. To expand the evidence further, we performed meta-analyses of the published data on these associations from prospective studies among the general population. Our study revealed a significant relationship between sCD30 concentration and BCL risk (OR=0.86, 1.53, 1.76, for the 2(nd) -4(th) quartiles respectively, P-trend=0.01). Similar increased risks were observed for diffuse large B-cell lymphoma and follicular lymphoma. Analyses of sCD27 blood concentrations did not show significant associations with BCL, (OR=0.90, 1.26, 1.65 for the 2(nd) -4(th) quartiles, respectively, P-trend=0.17), but significant associations were observed for chronic lymphocytic leukaemia and for the group of 'other BCL' subtypes. Our findings involving sCD30 were confirmed within our meta-analyses of five prospective cohorts, while results were more heterogeneous for sCD27 with the exception of CLL which was found consistently in all studies. Data to date suggest that chronic B-cell stimulation might be an important mechanism involved in B-cell lymphomagenesis both in HIV-infected and in the general population.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016. Vol. 138, no 10, p. 2357-2367
Keywords [en]
lymphoma, sCD30, sCD27, meta-analyses, prospective study
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-116971DOI: 10.1002/ijc.29969ISI: 000372257300006PubMedID: 26684261OAI: oai:DiVA.org:umu-116971DiVA, id: diva2:903667
Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2019-02-14Bibliographically approved
In thesis
1. Molecular epidemiology approach: nested case-control studies in glioma and lymphoid malignancies
Open this publication in new window or tab >>Molecular epidemiology approach: nested case-control studies in glioma and lymphoid malignancies
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

BACKGROUND: Nested case-control studies aim to link molecular markers with a certain outcome. Repeated prediagnostic samples may improve the evaluation of marker-disease associations. However, data regarding the benefit of repeated samples in such studies are sparse. We aimed to assess the relationship between blood levels of various proteins and risk of glioma, B cell lymphoma, and multiple myeloma to gain further understanding of disease etiology and to evaluate the clinical relevance of the studied markers. To this end, marker-disease associations were evaluated considering the natural history of the studied disease and the time between blood sample collection and diagnosis using both single (I-II) and repeated prediagnostic blood samples (III-IV).

PATIENTS AND METHODS: We conducted four nested case-control studies and one meta-analysis using samples from three prospective cohorts: the Janus Serum Bank, the Northern Sweden Health and Disease study, and the European Prospective Investigation into Cancer and Nutrition study. The following studied endpoints and relationships were included: I) glioma risk and the association with the receptor tyrosine kinases (soluble) sEGFR and sERBB2; II) B cell lymphoma risk and the association with the immune markers sCD27 and sCD30; III) B cell lymphoma risk and the association with immune markers (CXCL13, sTNF-R1, sCD23, sCD27, and sCD30) and their trends over time; and IV) multiple myeloma risk and the association  with ten immune markers and growth factors (MCP-3, MIP-1α, MIP-1β, VEGF, FGF-2, fractalkine, TGF-α, IL-13, TNF-α, and IL-10) and their trends over time.

RESULTS: Risk of developing I) glioma was weakly associated with high blood levels of sERBB2. In addition, high levels of both sEGFR and sERBB2 assessed 15 years before diagnosis were associated with glioblastoma risk.

Risk of II) B cell lymphoma was associated with high levels of sCD30, whereas high levels of sCD27 were particularly associated with risk of chronic lymphocytic leukemia. Meta-analyses showed consistent results for sCD30 across cohorts and lymphoma subtypes, whereas results for sCD27 were less consistent across cohorts and subtypes.

In addition, III) B cell lymphoma risk was associated with levels of CXCL13, sCD23, sCD27, and sCD30 assessed in samples collected 17 years before diagnosis. Marker levels increased in cases closer to diagnosis, particularly for indolent lymphoma with a marked association for chronic lymphocytic leukemia and sCD23. Increasing marker levels closer to diagnosis were also observed for CXCL13 in future diffuse large B cell lymphoma patients.

Risk of IV) multiple myeloma was associated with low levels of MCP-3, VEGF, FGF-2, fractalkine, and TGF-α. Levels of these markers decreased in myeloma cases over time, especially for TGF-α. TGF-α assessed at time of the prediagnostic repeated sample seemed to help predict progression to multiple myeloma.

CONCLUSIONS: Both the natural history of the studied disease and the time between sample collection and diagnosis are crucial for the evaluation of marker-disease associations. Using repeated blood samples improves the understanding of marker-disease associations and might help to identify useful biomarker candidates.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2019. p. 53
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2016
Keywords
Glioma, B cell lymphoma, multiple myeloma, risk, repeated samples, prospective longitudinal study, nested case-control study, circulating sEGFR and sERBB2, circulating immune markers and growth factors, marker disease association, disease progression, NSHDS, Janus, linear mixed modeling
National Category
Cancer and Oncology
Research subject
Epidemiology; Oncology
Identifiers
urn:nbn:se:umu:diva-156421 (URN)978-91-7855-025-8 (ISBN)
Public defence
2019-03-22, Bergasalen, byggnad 27, Norrlands universitetssjukhus, Umeå, 09:00 (English)
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Available from: 2019-02-22 Created: 2019-02-14 Last updated: 2019-02-21Bibliographically approved

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Späth, FlorentinBergdahl, Ingvar AMelin, Beatrice

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