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Hum Mol Genet. 2017 Jan 15;26(2):454-465. doi: 10.1093/hmg/ddw414.

Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations.

Seow WJ1,2, Matsuo K3, Hsiung CA4, Shiraishi K5, Song M1,6, Kim HN7, Wong MP8, Hong YC9, Hosgood HD 3rd10, Wang Z1,11, Chang IS12, Wang JC13,14, Chatterjee N1, Tucker M1, Wei H1, Mitsudomi T15, Zheng W16, Kim JH17, Zhou B18, Caporaso NE1, Albanes D1, Shin MH7, Chung LP8, An SJ19, Wang P20, Zheng H21, Yatabe Y22, Zhang XC19, Kim YT23, Shu XO16, Kim YC24,25, Bassig BA1, Chang J26, Ho JC27, Ji BT1, Kubo M28, Daigo Y29,30, Ito H31, Momozawa Y28, Ashikawa K28, Kamatani Y32, Honda T5, Sakamoto H33, Kunitoh H34, Tsuta K35, Watanabe SI36, Nokihara H37, Miyagi Y38, Nakayama H39, Matsumoto S40, Tsuboi M41, Goto K42, Yin Z18, Shi J1, Takahashi A32, Goto A43, Minamiya Y44, Shimizu K45, Tanaka K45, Wu T46, Wei F47, Wong JY1, Matsuda F48, Su J19, Kim YH49, Oh IJ24,25, Song F21, Lee VH50, Su WC51, Chen YM52,53, Chang GC54,55, Chen KY56, Huang MS57, Yang PC58, Lin HC4, Xiang YB59, Seow A2, Park JY60, Kweon SS7,61, Chen CJ62, Li H21, Gao YT59, Wu C63, Qian B21, Lu D13,14, Liu J2,64,65, Jeon HS66, Hsiao CF4, Sung JS49, Tsai YH67, Jung YJ23, Guo H46, Hu Z68, Wang WC69, Chung CC1,70, Lawrence C71, Burdett L1,70, Yeager M1,70, Jacobs KB1,70, Hutchinson A1,70, Berndt SI1, He X72, Wu W18, Wang J73,74, Li Y75, Choi JE66, Park KH49, Sung SW76, Liu L77, Kang CH23, Hu L78,79, Chen CH12, Yang TY55, Xu J80, Guan P18,81, Tan W63, Wang CL82, Sihoe AD83, Chen Y2, Choi YY66, Hung JY57, Kim JS84, Yoon HI85, Cai Q16, Lin CC51, Park IK23, Xu P86, Dong J78,79, Kim C1, He Q18, Perng RP87, Chen CY88,89, Vermeulen R90, Wu J13,14, Lim WY91, Chen KC55, Chan JK92, Chu M78,79, Li YJ62, Li J93, Chen H13,14, Yu CJ58, Jin L13,14, Lo YL4, Chen YH4, Fraumeni JF Jr1, Liu J94, Yamaji T95, Yang Y96, Hicks B1,70, Wyatt K1,70, Li SA1,70, Dai J68, Ma H68, Jin G68, Song B94, Wang Z94, Cheng S94, Li X18,81, Ren Y18,81, Cui P21, Iwasaki M95, Shimazu T95, Tsugane S95, Zhu J96, Jiang G96, Fei K96, Wu G47, Chien LH4, Chen HL4, Su YC4, Tsai FY12, Chen YS4, Yu J94, Stevens VL97, Laird-Offringa IA98, Marconett CN98, Lin D63, Chen K21, Wu YL19, Landi MT1, Shen H68,99, Rothman N1, Kohno T5, Chanock SJ1, Lan Q1.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
2
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
3
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
4
Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
5
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
6
Department of Statistics, Sookmyung Women's University, Seoul, Republic of Korea.
7
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
8
Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
9
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
10
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
11
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
12
National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
13
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
14
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
15
Division of Thoracic Surgery, Kinki University School of Medicine, Sayama, Japan.
16
Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
17
Department of Integrative Bioscience & Biotechnology, Sejong University, Seoul, Republic of Korea.
18
Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China.
19
Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
20
Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.
21
Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
22
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, Nagoya, Japan.
23
Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
24
Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea.
25
Department of Internal Medicine, Chonnam National Univerisity Medical School, Gwangju, Republic of Korea.
26
Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
27
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.
28
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
29
Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
30
Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Otsu, Japan.
31
Division of Epidemiology & Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
32
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
33
Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
34
Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
35
Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.
36
Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
37
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
38
Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa, Japan.
39
Department of Thoracic Surgery, Kanagawa Cancer Center, Kanagawa, Japan.
40
Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Chiba, Japan.
41
Department of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan.
42
Department of Thoracic Oncology, National Cancer Center Hospital East, Japan.
43
Department of Cellular and Organ Pathology.
44
Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita City, Japan.
45
Department of Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan.
46
Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
47
China National Environmental Monitoring Center, Beijing, People's Republic of China.
48
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
49
Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
50
Department of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
51
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
52
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
53
College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
54
School of Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
55
Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
56
Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
57
Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
58
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
59
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China.
60
Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
61
Jeonnam Regional Cancer Center, Chonnam National University Hwasun, Hwasun Hospital, Republic of Korea.
62
Genomic Research Center, Academia Sinica, Taipei, Taiwan.
63
Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
64
Department of Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
65
School of Life Sciences, Anhui Medical University, Hefei, People's Republic of China.
66
Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
67
Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
68
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
69
The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
70
Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc, Gaithersburg, MD, USA.
71
Westat, Rockville, MD, USA.
72
Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
73
Department of Health Sciences Research.
74
Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ, USA.
75
Cancer Prevention Institute of California, Fremont, CA, USA.
76
Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, Republic of Korea.
77
Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
78
Ministry of Education Key Laboratory of Modern Toxicology.
79
Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, People's Republic of China.
80
School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
81
Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, People's Republic of China.
82
Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
83
Department of Surgery, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
84
Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
85
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
86
Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, People's Republic of China.
87
Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan.
88
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
89
Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
90
Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
91
Agency for Integrated Care, Singapore.
92
Department of Pathology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China.
93
Qujing Center for Diseases Control and Prevention, Qujing, People's Republic of China.
94
Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
95
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
96
Shanghai Pulmonary Hospital, Shanghai, People's Republic of China.
97
Laboratory Services, American Cancer Society, Atlanta, GA, USA.
98
Department of Surgery, Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
99
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.

Abstract

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (Pā€‰<ā€‰5 Ɨ 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.

PMID:
28025329
PMCID:
PMC5856088
DOI:
10.1093/hmg/ddw414
[Indexed for MEDLINE]
Free PMC Article

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