Oncotarget

Research Papers:

Higher frequency but random distribution of EGFR mutation subtypes in familial lung cancer patients

Kuo-Hsuan Hsu, Jeng-Sen Tseng, Chih-Liang Wang, Tsung-Ying Yang, Chien-Hua Tseng, Hsuan-Yu Chen, Kun-Chieh Chen, Chi-Ren Tsai, Cheng-Ta Yang, Sung-Liang Yu, Kang-Yi Su, Chong-Jen Yu, Chao-Chi Ho, Te-Chun Hsia, Ming-Fang Wu, Kuo-Liang Chiu, Chien-Ming Liu, Pan-Chyr Yang, Jeremy J.W. Chen and Gee-Chen Chang _

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Oncotarget. 2016; 7:53299-53308. https://doi.org/10.18632/oncotarget.10715

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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: august@vghtc.gov.tw

Jeremy J.W. Chen, email: jwchen@dragon.nchu.edu.tw

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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