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To improve timely detection of MM in asbestos workers, better screening tools \u2013 like minimally-invasive biomarkers \u2013 are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.<\/jats:p>","DOI":"10.1038\/s41598-018-32315-3","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T09:49:41Z","timestamp":1537350581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin \u2013 a case-control comparison nested into a prospective cohort of asbestos-exposed 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