Germline mutations in young non-smoking women with lung adenocarcinoma.

Autor: Donner I; Department of Medical and Clinical Genetics, Medicum, and Genome-Scale Biology Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Katainen R; Department of Medical and Clinical Genetics, Medicum, and Genome-Scale Biology Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Sipilä LJ; Department of Medical and Clinical Genetics, Medicum, and Genome-Scale Biology Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Aavikko M; Department of Medical and Clinical Genetics, Medicum, and Genome-Scale Biology Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Pukkala E; Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland; Faculty of Social Sciences, University of Tampere, Tampere, Finland., Aaltonen LA; Department of Medical and Clinical Genetics, Medicum, and Genome-Scale Biology Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: lauri.aaltonen@helsinki.fi.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2018 Aug; Vol. 122, pp. 76-82. Date of Electronic Publication: 2018 May 31.
DOI: 10.1016/j.lungcan.2018.05.027
Abstrakt: Objectives: Although the primary cause of lung cancer is smoking, a considerable proportion of all lung cancers occur in never smokers. Gender influences the risk and characteristics of lung cancer and women are overrepresented among never smokers with the disease. Young age at onset and lack of established environmental risk factors suggest genetic predisposition. In this study, we used population-based sampling of young patients to discover candidate predisposition variants for lung adenocarcinoma in never-smoking women.
Materials and Methods: We employed archival normal tissue material from 21 never-smoker women who had been diagnosed with lung adenocarcinoma before the age of 45, and exome sequenced their germline DNA.
Results and Conclusion: Potentially pathogenic variants were found in eight Cancer Gene Census germline genes: BRCA1, BRCA2, ERCC4, EXT1, HNF1 A, PTCH1, SMARCB1 and TP53. The variants in TP53, BRCA1, and BRCA2 are likely to have contributed to the early onset lung cancer in the respective patients (3/21 or 14%). This supports the notion that lung adenocarcinoma can be a component of certain cancer predisposition syndromes. Fifteen genes displayed potentially pathogenic mutations in at least two patients: ABCC10, ATP7B, CACNA1S, CFTR, CLIP4, COL6A1, COL6A6, GCN1, GJB6, RYR1, SCN7A, SEC24A, SP100, TTN and USH2A. Four patients showed a mutation in COL6A1, three in CLIP4 and two in the rest of the genes. Some of these candidate genes may explain a subset of female lung adenocarcinoma.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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