Germline mutations in young non-smoking women with lung adenocarcinoma

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http://hdl.handle.net/10138/239086

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Donner , I , Katainen , R , Sipilä , L J , Aavikko , M , Pukkala , E & Aaltonen , L A 2018 , ' Germline mutations in young non-smoking women with lung adenocarcinoma ' , Lung Cancer , vol. 122 , pp. 76-82 . https://doi.org/10.1016/j.lungcan.2018.05.027

Title: Germline mutations in young non-smoking women with lung adenocarcinoma
Author: Donner, Iikki; Katainen, Riku; Sipilä, Lauri J.; Aavikko, Mervi; Pukkala, Eero; Aaltonen, Lauri A.
Contributor organization: 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
Doctoral Programme in Integrative Life Science
Date: 2018-08
Language: eng
Number of pages: 7
Belongs to series: Lung Cancer
ISSN: 0169-5002
DOI: https://doi.org/10.1016/j.lungcan.2018.05.027
URI: http://hdl.handle.net/10138/239086
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 over-represented 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: BRCAI, BRCA2, ERCC4, EXT1, HNF1 A, PTCH1, SMARCB1 and TP53. The variants in TP53, BRCAI, 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, TEN 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.
Subject: Lung adenocarcinoma
Never smoker
Women
Exome sequencing
Early onset
Genetic predisposition to cancer
LI-FRAUMENI-SYNDROME
NEVER-SMOKERS
SUSCEPTIBILITY LOCUS
CANCER RISK
VI COLLAGEN
VARIANTS
BRCA2
EGFR
FIBROSIS
PREDISPOSITION
3122 Cancers
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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