DNA hypermethylation analysis in sputum of asymptomatic subjects at risk for lung cancer participating in the NELSON trial: argument for maximum screening interval of 2years
| Autor: | Anne M. Uyterlinde, Clemens F.M. Prinsen, Harry J.M. Groen, Susanne E van der Meer, Anne S. Bolijn, Hans Berkhof, Harry J. de Koning, A. Jasmijn Hubers, Renske D.M. Steenbergen, Birgit I. Witte, Mandy Wouters, Daniëlle A.M. Heideman, Peter J.F. Snijders, Erik Thunnissen, Sylvia Duin, Egbert F. Smit |
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| Přispěvatelé: | Public Health, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Pathology, CCA - Clinical Therapy Development, Epidemiology and Data Science, Pulmonary medicine |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Sputum Cytology medicine.medical_specialty Pathology Lung Neoplasms Disease ONCOGENES DIAGNOSIS Polymerase Chain Reaction Sensitivity and Specificity Asymptomatic Gastroenterology Pathology and Forensic Medicine law.invention 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being law Internal medicine SPUTUM Biomarkers Tumor medicine Humans Lung cancer Early Detection of Cancer Polymerase chain reaction Aged Lung business.industry Tumor Suppressor Proteins General Medicine LUNG CANCER DNA Methylation Middle Aged medicine.disease 030104 developmental biology medicine.anatomical_structure PCR PROMOTER HYPERMETHYLATION 030220 oncology & carcinogenesis Sputum Female medicine.symptom business Lung cancer screening SMOKERS CT |
| Zdroj: | Journal of Clinical Pathology, 70(3), 250-254. BMJ Publishing Group Journal of Clinical Pathology, 70(3), 250-254. BMJ PUBLISHING GROUP Journal of Clinical Pathology. BMJ Publishing Group Hubers, A J, Heideman, D A M, Duin, S, Witte, B I, de Koning, H J, Groen, H J M, Prinsen, C F M, Bolijn, A S, Wouters, M, van der Meer, S E, Steenbergen, R D M, Snijders, P J F, Uyterlinde, A, Berkhof, H, Smit, E F & Thunnissen, E 2016, ' DNA hypermethylation analysis in sputum of asymptomatic subjects at risk for lung cancer participating in the NELSON trial : argument for maximum screening interval of 2 years ', Journal of Clinical Pathology . https://doi.org/10.1136/jclinpath-2016-203734 |
| ISSN: | 0021-9746 |
| DOI: | 10.1136/jclinpath-2016-203734 |
| Popis: | AIMS: Lung cancer is the major contributor to cancer mortality due to metastasised disease at time of presentation. The current study investigated DNA hypermethylation of biomarkers RASSF1A, APC, cytoglobin, 3OST2, FAM19A4, PHACTR3 and PRDM14 in sputum of asymptomatic high-risk individuals from the NELSON lung cancer low-dose spiral CT screening trial to detect lung cancer at preclinical stage.METHODS: Subjects were selected with (i) lung cancer in follow-up (cases; n=65), (ii) minor cytological aberrations (controls; n=120) and (iii) a random selection of subjects without cytological aberrations (controls; n=99). Median follow-up time for controls was 80 months. Cut-off values were based on high specificity to assess diagnostic value of the biomarkers.RESULTS: RASSF1A may denote presence of invasive cancer because of its high specificity (93% (95% CI 89% to 96%); sensitivity 17% (95% CI 4% to 31%), with best performance in a screening interval of 2 years. The panel of RASSF1A, 3OST2 and PRDM14 detected 28% (95% CI 11% to 44%) of lung cancer cases within 2 years, with specificity of 90% (95% CI 86% to 94%). Sputum cytology did not detect any lung cancers.CONCLUSIONS: In a lung cancer screening setting with maximum screening interval of 2 years, DNA hypermethylation analysis in sputum may play a role in the detection of preclinical disease, but complementary diagnostic markers are needed to improve sensitivity. |
| Databáze: | OpenAIRE |
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