Soluble B-Cell Activation Marker Of sCD27 And sCD30 And Future Risk Of B-Cell Lymphomas: A Nested Case-Control Study And Meta-Analyses

Roel VERMEULEN, Utrecht University, Netherlands
SABERI HOSNIJEH F. 1,3 , PORTENGEN L. 1 , SP─TH F. 3 , BERGDAHL I. 4,5 , MELIN B. 3 , MATTIELLO A. 6 , MASALA G. 7 , SACERDOTE C. 8 , NACCARATI A. 9 , KROGH V. 10 , TUMINO R. 11 , CHADEAU-HYAM M. 12 , VINEIS P. 9, 12

1 Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Utrecht, the Netherlands
2 Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
3 Department of Radiation Sciences, Oncology, Umeň University, Umeň, Sweden
4 Department of Biobank Research, Umeň University, Umeň, Sweden
5 Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeň University, Umeň, Sweden
6 Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
7 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy
8 Unit of Cancer Epidemiology, AO Citta' della Salute e della Scienza, University of Turin and Center for Cancer Prevention, Turin, Italy
9 Human Genetics Foundation-HUGEF, Turin, Italy
10 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
11 Cancer Registry and Histopathology Unit, "CIVIC - M.P.AREZZO" Hospital, ASP Ragusa, Italy
12 Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

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 2nd-4th 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 2nd-4th 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.