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Germline mutations in young non-smoking women with lung adenocarcinoma
- Source :
- Lung Cancer. 122:76-82
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
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.
- 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
Subjects
Details
- ISSN :
- 01695002
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Lung Cancer
- Accession number :
- edsair.doi.dedup.....2894a93afa79d9c8e63daa27acbf44d6