Serum levels of hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study

Delphine Casabonne*, Yolanda Benavente, Julia Seifert, Laura Costas, María Armesto, María Arestin, Caroline Besson, Fatemeh S. Hosnijeh, Eric J. Duell, Elisabete Weiderpass, Giovanna Masala, Rudolf Kaaks, Federico Canzian, María Dolores Chirlaque, Vittorio Perduca, Francesca R. Mancini, Valeria Pala, Antonia Trichopoulou, Anna Karakatsani, Carlo La VecchiaMaria Jose Sánchez, Rosario Tumino, Marc J. Gunter, Pilar Amiano, Salvatore Panico, Carlotta Sacerdote, Julie A. Schmidt, Heiner Boeing, Matthias B. Schulze, Aurelio Barricarte, Elio Riboli, Anja Olsen, Anne Tjønneland, Roel Vermeulen, Alexandra Nieters, Charles H. Lawrie, Silvia de Sanjosé

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Chronic lymphocytic leukemia (CLL) is an incurable disease accounting for almost one-third of leukemias in the Western world. Aberrant expression of microRNAs (miRNAs) is a well-established characteristic of CLL, and the robust nature of miRNAs makes them eminently suitable liquid biopsy biomarkers. Using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), the predictive values of five promising human miRNAs (hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p), identified in a pilot study, were examined in serum of 224 CLL cases (diagnosed 3 months to 18 years after enrollment) and 224 matched controls using Taqman based assays. Conditional logistic regressions were applied to adjust for potential confounders. The median time from blood collection to CLL diagnosis was 10 years (p25–p75: 7–13 years). Overall, the upregulation of hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p was associated with subsequent risk of CLL [OR1∆Ct-unit increase (95%CI) = 1.42 (1.18–1.72), 1.64 (1.31–2.04) and 1.75 (1.31–2.34) for hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p, respectively] and the strongest associations were observed within 10 years of diagnosis. However, the predictive performance of these miRNAs was modest (area under the curve <0.62). hsa-miR-16-5p and hsa-miR-223-3p levels were unrelated to CLL risk. The findings of this first prospective study suggest that hsa-miR-29a, hsa-miR-150-5p and hsa-miR-155-5p were upregulated in early stages of CLL but were modest predictive biomarkers of CLL risk.

Original languageEnglish
Pages (from-to)1315-1324
Number of pages10
JournalInternational Journal of Cancer
Volume147
Issue number5
DOIs
Publication statusPublished - 1 Sept 2020

Funding

We thank all participants of the EPIC study, Bertrand H?mon at IARC for his valuable work and technical support with the EPIC database. The authors would like to thank the participants of the EpiLymph-Spain study as well as Dr Eva Domingo (Catalan Institute of Oncology, l'Hospitalet de Llobregat, Spain) and Dr Ram?n Bosch (Hospital de Tortosa Verge de la Cinta, Tortosa, Spain) for their support in patient recruitment. The Ume?-EPIC node at Ume? University, Sweden is acknowledged for their valuable contribution and ongoing support to the EPIC Study. We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study. The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) is grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. Our study was supported by the : European Commission (DG-SANCO), International Agency for Research on Cancer, Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (EPIC-Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study, World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands; ERC2009-AdG 232997), German Federal Ministry of Education and Research (BMBF 01EO1303), Spanish Ministry of Economy and Competitiveness?Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF)?a way to build Europe (PI13/00061 [to Granada], PI13/01162 [to EPICMurcia, Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra], PI17/01280 and PI14/01219 [to Barcelona]), Centro de Investigaci?n Biom?dica en Red: Epidemiolog?a y Salud P?blica (CIBERESP, Spain), Ag?ncia de Gesti? d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme/Generalitat de Catalunya for institutional support (2017SGR1085), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and Vasterbotten (Sweden), Cancer Research UK (14136 [to EPIC-Norfolk], C8221/A19170 [to EPIC-Oxford]) and Medical Research Council Canada (MR/N003284/1, MC-PC_13048 and MC-UU_12015/1 [to EPIC-Norfolk study; doi: 10.22025/2019.10.105.00004), MR/M012190/1 [to EPIC-Oxford, UK]).

Keywords

  • chronic lymphocytic leukemia
  • circulating miRNA
  • prospective study
  • serum

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