1. Germline mutations in young non-smoking women with lung adenocarcinoma
- Author
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Eero Pukkala, Iikki Donner, Lauri A. Aaltonen, Lauri J. Sipilä, Riku Katainen, Mervi Aavikko, University of Helsinki, Research Programmes Unit, University of Helsinki, Medicum, Research Programs Unit, Genome-Scale Biology (GSB) Research Program, University of Helsinki, Faculty of Medicine, Department of Medical and Clinical Genetics, Medicum, Lauri Antti Aaltonen / Principal Investigator, and Doctoral Programme in Integrative Life Science
- Subjects
Lung adenocarcinoma ,0301 basic medicine ,Oncology ,Cancer Research ,Candidate gene ,Lung Neoplasms ,DNA Mutational Analysis ,VARIANTS ,0302 clinical medicine ,FIBROSIS ,SUSCEPTIBILITY LOCUS ,Exome ,education.field_of_study ,BRCA1 Protein ,Never smoker ,Genetic predisposition to cancer ,3. Good health ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Female ,LI-FRAUMENI-SYNDROME ,Adult ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Genotype ,EGFR ,3122 Cancers ,Population ,Adenocarcinoma of Lung ,3121 Internal medicine ,Cigarette Smoking ,Young Adult ,03 medical and health sciences ,Germline mutation ,Internal medicine ,Exome Sequencing ,medicine ,Genetic predisposition ,Humans ,Women ,Genetic Predisposition to Disease ,education ,Lung cancer ,VI COLLAGEN ,Germ-Line Mutation ,BRCA2 Protein ,CANCER RISK ,business.industry ,Membrane Proteins ,medicine.disease ,BRCA2 ,PREDISPOSITION ,respiratory tract diseases ,030104 developmental biology ,NEVER-SMOKERS ,Li–Fraumeni syndrome ,3121 General medicine, internal medicine and other clinical medicine ,Carrier Proteins ,business ,Early onset - Abstract
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.
- Published
- 2018