Research Papers:
Higher frequency but random distribution of EGFR mutation subtypes in familial lung cancer patients
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Abstract
Kuo-Hsuan Hsu1,2, Jeng-Sen Tseng3,4, Chih-Liang Wang5,6, Tsung-Ying Yang3,4, Chien-Hua Tseng7,8, Hsuan-Yu Chen9,10,11, Kun-Chieh Chen3, Chi-Ren Tsai12,13, Cheng-Ta Yang5,14, Sung-Liang Yu15,16,17,18,19, Kang-Yi Su15,16, Chong-Jen Yu20, Chao-Chi Ho20, Te-Chun Hsia21,22, Ming-Fang Wu23,24, Kuo-Liang Chiu25,26, Chien-Ming Liu25, Pan-Chyr Yang20, Jeremy J.W. Chen1, Gee-Chen Chang1,3,4
1Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
2Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
3Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
4Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
5Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
6College of Medicine, Chang Gung University, Taoyuan, Taiwan
7Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
8Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
9Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
10College of Medicine, National Taiwan University, Taipei, Taiwan
11College of Life Science, National Taiwan University, Taipei, Taiwan
12Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan
13Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan
14Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan, Taiwan
15Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
16Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
17Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan
18Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
19Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan
20Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
21Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
22Department of Respiratory Therapy, China Medical University, Taichung, Taiwan
23Divisions of Medical Oncology and Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
24School of Medicine, Chung Shan Medical University, Taichung, Taiwan
25Division of Chest Medicine, Department of Internal Medicine, Taichung Tzu-Chi Hospital, Taichung, Taiwan
26School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
Correspondence to:
Gee-Chen Chang, email: [email protected]
Jeremy J.W. Chen, email: [email protected]
Keywords: familial lung cancer, epidermal growth factor receptor (EGFR), non-small cell lung cancer, YAP1
Received: May 09, 2016 Accepted: June 30, 2016 Published: July 19, 2016
ABSTRACT
Despite the advancement of epidermal growth factor receptor (EGFR) inhibitors in lung cancer therapy, it remains unclear whether EGFR mutation status in familial lung cancers is different from that of sporadic cases. In this multicenter retrospective study, we compared both the EGFR mutation frequency and patterns between familial and sporadic cases. The results explored that family history of lung cancer is an independent predictor for higher EGFR mutation rate in 1713 lung adenocarcinoma patients (Odd ratio 1.68, 95% CI 1.06–2.67, P = 0.028). However, the distribution of EGFR mutation subtypes was similar to that of sporadic cases. Part of our study involved 40 lung cancer families with at least 2 tumor tissues available within each single family (n = 88) and there was no familial aggregation pattern in EGFR mutation subtypes. There were two families harboring the YAP1 R331W germline risk allele and EGFR mutation statuses among YAP1 family members also varied. These phenomena may hint at the direction of future research into lung carcinogenesis and EGFR mutagenesis.
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