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Casabonne, Delphine; Benavente, Yolanda; Seifert, Julia; Costas, Laura; Armesto, María; Arestin, María; Besson, Caroline; Hosnijeh, Fatemeh S.; Duell, Eric J.; Weiderpass, Elisabete; Masala, Giovanna; Kaaks, Rudolf; Canzian, Federico; Chirlaque, María‐Dolores; Perduca, Vittorio; Mancini, Francesca R.; Pala, Valeria; Trichopoulou, Antonia; Karakatsani, Anna; La Vecchia, Carlo; Sánchez, Maria‐Jose; Tumino, Rosario; Gunter, Marc J.; Amiano, Pilar; Panico, Salvatore; Sacerdote, Carlotta; Schmidt, Julie A.; Boeing, Heiner; Schulze, Matthias B.; Barricarte, Aurelio; Riboli, Elio; Olsen, Anja; Tjønneland, Anne; Vermeulen, Roel; Nieters, Alexandra; Lawrie, Charles H.; Sanjosé, Silvia
International journal of cancer, 1 September 2020, Volume: 147, Issue: 5Journal Article
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. What's new? Aberrant circulating microRNA (miRNA) levels are a well‐established characteristic of chronic lymphocytic leukemia (CLL), but pre‐diagnosis data remain scarce. In this nested case–control study within the European Prospective Investigation into Cancer and Nutrition Study, circulating hsa‐miRNA‐29a‐3p, ‐150‐5p, and ‐155‐5p were upregulated up to 10 years before CLL diagnosis compared to controls, suggesting a role in early disease progression. However, these biomarkers were suboptimal to discriminate CLL from controls. No difference was observed in hsa‐miRNA‐16‐5p and ‐223‐3p expression between pre‐CLL and controls. The ability to detect pre‐clinical biomarkers may help better understand CLL development and open new avenues for personalized treatment.
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