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Hum Mol Genet. 2016 Feb 1;25(3):620-9. doi: 10.1093/hmg/ddv494. Epub 2016 Jan 4.

Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women.

Wang Z1, Seow WJ2, Shiraishi K3, Hsiung CA4, Matsuo K5, Liu J6, Chen K7, Yamji T8, Yang Y9, Chang IS10, Wu C11, Hong YC12, Burdett L13, Wyatt K13, Chung CC13, Li SA13, Yeager M13, Hutchinson A13, Hu W2, Caporaso N2, Landi MT2, Chatterjee N2, Song M2, Fraumeni JF Jr2, Kohno T3, Yokota J14, Kunitoh H15, Ashikawa K16, Momozawa Y16, Daigo Y17, Mitsudomi T18, Yatabe Y19, Hida T20, Hu Z21, Dai J21, Ma H21, Jin G21, Song B6, Wang Z6, Cheng S6, Yin Z22, Li X22, Ren Y22, Guan P22, Chang J11, Tan W11, Chen CJ23, Chang GC24, Tsai YH25, Su WC26, Chen KY27, Huang MS28, Chen YM29, Zheng H7, Li H7, Cui P7, Guo H30, Xu P31, Liu L32, Iwasaki M8, Shimazu T8, Tsugane S8, Zhu J9, Jiang G9, Fei K9, Park JY33, Kim YH34, Sung JS34, Park KH34, Kim YT35, Jung YJ35, Kang CH35, Park IK35, Kim HN36, Jeon HS37, Choi JE37, Choi YY37, Kim JH38, Oh IJ39, Kim YC39, Sung SW40, Kim JS41, Yoon HI42, Kweon SS43, Shin MH44, Seow A45, Chen Y45, Lim WY45, Liu J46, Wong MP47, Lee VH48, Bassig BA2, Tucker M2, Berndt SI2, Chow WH2, Ji BT2, Wang J49, Xu J50, Sihoe AD51, Ho JC52, Chan JK53, Wang JC54, Lu D54, Zhao X54, Zhao Z54, Wu J54, Chen H54, Jin L54, Wei F55, Wu G55, An SJ56, Zhang XC56, Su J56, Wu YL56, Gao YT57, Xiang YB57, He X58, Li J59, Zheng W60, Shu XO60, Cai Q60, Klein R61, Pao W62, Lawrence C63, Hosgood HD 3rd64, Hsiao CF4, Chien LH4, Chen YH4, Chen CH10, Wang WC65, Chen CY66, Wang CL67, Yu CJ68, Chen HL4, Su YC4, Tsai FY10, Chen YS4, Li YJ23, Yang TY69, Lin CC26, Yang PC68, Wu T30, Lin D11, Zhou B22, Yu J6, Shen H21, Kubo M16, Chanock SJ2, Rothman N2, Lan Q2.

Author information

1
Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Gaithersburg, MD, USA, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA, wangzha@mail.nih.gov.
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
3
Division of Genome Biology, National Cancer Center Hospital, Tokyo, Japan.
4
Institute of Population Health Sciences.
5
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
6
Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China.
7
Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
8
Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
9
Shanghai Pulmonary Hospital, Shanghai, China.
10
National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
11
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, China.
12
Department of Preventive Medicine.
13
Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Gaithersburg, MD, USA, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
14
Cancer Genome Biology Group, Institute of Predictive and Personalized Medicine of Cancer, Barcelona, Spain.
15
Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
16
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
17
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
18
Division of Thoracic Surgery, Kinki University School of Medicine, Sayama, Japan.
19
Department of Pathology and Molecular Diagnostics.
20
Department of Thoracic Oncology, Aichi Cancer Center Central Hospital, Nagoya, Japan.
21
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, China.
22
Department of Epidemiology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, China, Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China.
23
Genomic Research Center, Academia Sinica, Taipei, Taiwan.
24
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
25
Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
26
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
27
Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
28
Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
29
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, College of Medical Science and Technology.
30
Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College.
31
Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, China.
32
Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
33
Lung Cancer Center.
34
Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
35
Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
36
Center for Creative Biomedical Scientists, Chonnam National University, Gwangju, Republic of Korea.
37
Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
38
Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
39
Lung and Esophageal Cancer Clinic, Department of Internal Medicine.
40
Department of Thoracic and Cardiovascular Surgery.
41
Department of Internal Medicine, Division of Medical Oncology, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
42
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
43
Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea, Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
44
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
45
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
46
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore, Department of Human Genetics, Genome Institute of Singapore, Singapore, Singapore, School of Life Sciences, Anhui Medical University, Hefei, China.
47
Department of Pathology, Li Ka Shing (LKS) Faculty of Medicine.
48
Department of Clinical Oncology, LKS Faculty of Medicine.
49
Department of Biochemistry, LKS Faculty of Medicine, Centre for Genomic Sciences, LKS Faculty of Medicine.
50
School of Public Health, Li Ka Shing (LKS) Faculty of Medicine.
51
Department of Surgery, Li Ka Shing (LKS) Faculty of Medicine.
52
Department of Medicine, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
53
Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China.
54
Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
55
China National Environmental Monitoring Center, Beijing, China.
56
Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
57
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
58
Chinese Center for Disease Control and Prevention, Beijing, China.
59
Qujing Center for Diseases Control and Prevention, Sanjiangdadao, Qujing, China.
60
Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
61
Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
62
Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
63
Westat, Rockville, MD, USA.
64
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
65
The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
66
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan and.
67
Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
68
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
69
Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Abstract

Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 × 10(-13)), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 × 10(-10)) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 × 10(-9)). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.

PMID:
26732429
PMCID:
PMC4731021
DOI:
10.1093/hmg/ddv494
[Indexed for MEDLINE]
Free PMC Article

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