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Int J Cancer. 2015 Jul 15;137(2):311-9. doi: 10.1002/ijc.29393. Epub 2014 Dec 29.

Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: a report from the female lung cancer consortium in Asia.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
2
Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
3
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
4
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.
5
Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
6
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
7
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
8
Saw Swee Hock School of Public Health, National University of Singapore, Republic of Singapore.
9
Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
10
State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
11
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
12
Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Medical University Cancer Institute and Hospital, Tianjin, China.
13
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
14
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
15
Department of Human Genetics, University of Utah, Salt Lake City, UT.
16
Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
17
Genomic Research Center, Taipei, Taiwan.
18
Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
19
Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
20
Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
21
Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
22
Westat, Rockville, MD.
23
National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
24
Division of Thoracic Surgery, Kinki University School of Medicine, Sayama, Japan.
25
Center for Creative Biomedical Scientists, Chonnam National University, Gwangju, Republic of Korea.
26
Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
27
Department of Internal Medicine, Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
28
Division of Environmental Health Sciences, Yale School of Public Health, New Haven, CT.
29
China National Environmental Monitoring Center, Beijing, China.
30
Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
31
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
32
Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University, Shanghai, China.
33
Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong, Kong, China.
34
Department of Human Genetics, Genome Institute of Singapore, Republic of Singapore.
35
School of Life Sciences, Anhui Medical University, Hefei, China.
36
Molecular Diagnostics and Imaging Center, Kyungpook National University, Daegu, Republic of Korea.
37
Taiwan Lung Cancer Tissue/Specimen Information Resource Center, National Health Research Institutes, Zhunan, Taiwan.
38
Cancer Research Institute, Korea University, Seoul, Republic of Korea.
39
Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
40
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
41
Department of Respiratory Thearpy, Chang Gung Memorial Hospital, Chiayi, Taiwan.
42
Institute of Occupational Medicine and Ministry of Education Key Lab for Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China.
43
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Icahn Institute for Genomics and Multiscale Biology, New York, NY.
44
Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-Eup, Republic of Korea.
45
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
46
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
47
Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
48
Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
49
Department of Biochemistry, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
50
Cancer Prevention Institute of California, Fremont, CA.
51
Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
52
Department of Internal Medicine, Cancer Center, National Cheng Kung University Hospital, National College of Medicine, Cheng Kung University, Tainan, Taiwan.
53
Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, Seoul, Republic of Korea.
54
Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
55
Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
56
Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
57
Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN.
58
School of Public Health, the University of Hong Kong, Hong Kong.
59
Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
60
Department of Surgery, Division of Cardiothoracic Surgery, Queen Mary Hospital, Hong Kong, China.
61
Department of Internal Medicine, Division of Medical Oncology, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
62
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
63
Department of Oncology, Wuhan Iron and Steel Corporation Staff Worker Hospital, Wuhan, China.
64
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
65
Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun-Eup, Republic of Korea.
66
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
67
Institute of Medicine, Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University, Chung Shan Medical University Hospital, Taichung, Taiwan.
68
Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
69
Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China.
70
Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain.
71
Qujing Center for Diseases Control and Prevention, Sanjiangdadao, Qujing, China.
72
Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
73
Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
74
Department of Pathology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
75
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

Abstract

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.

KEYWORDS:

association study; genetic risk score; genetics; lung cancer; telomere length

PMID:
25516442
PMCID:
PMC4733320
DOI:
10.1002/ijc.29393
[Indexed for MEDLINE]
Free PMC Article
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