G enetic 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
Open accessAbstract
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.
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Longer telomere length is associated with increased risk of B cell lymphoma and chronic lymphocytic leukaemia.
“Another observation in support of the telomere tumour suppressor pathway is that longer telomere length has been associated with an increased risk of B cell lymphoma and chronic lymphocytic leukaemia (CLL)65–67.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [65]
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Telomeres in cancer: tumour suppression and genome instability
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- Authors
- Machiela, M. J., Hsiung, C. A., Shu, X., Seow, W. J., Wang, Z., Matsuo, K., Hong, Y., Seow, A., Wu, C., Hosgood, H. D., Chen, K., Wang, J., Wen, W., Cawthon, R., Chatterjee, N., Hu, W., Caporaso, N. E., Park, J. Y., Chen, C., Kim, Y. H., Kim, Y. T., Landi, M. T., Shen, H., Lawrence, C., Burdett, L., Yeager, M., Chang, I., Mitsudomi, T., Kim, H. N., Chang, G., Bassig, B. A., Tucker, M., Wei, F., Yin, Z., An, S., Qian, B., Lee, V. H. F., Lu, D., Liu, J., Jeon, H., Hsiao, C., Sung, J. S., Kim, J. H., Gao, Y., Tsai, Y., Jung, Y. J., Guo, H., Hu, Z., Hutchinson, A., Wang, W., Klein, R. J., Chung, C. C., Oh, I., Chen, K., Berndt, S. I., Wu, W., Chang, J., Zhang, X., Huang, M., Zheng, H., Wang, J., Zhao, X., Li, Y., Choi, J. E., Su, W., Park, K. H., Sung, S. W., Chen, Y., Liu, L., Kang, C. H., Hu, L., Chen, C., Pao, W., Kim, Y., Yang, T., Xu, J., Guan, P., Tan, W., Su, J., Wang, C., Li, H., Sihoe, A. D. L., Zhao, Z., Chen, Y., Choi, Y. Y., Hung, J., Kim, J. S., Yoon, H., Cai, Q., Lin, C., Park, I. K., Xu, P., Dong, J., Kim, C., He, Q., Perng, R., Kohno, T., Kweon, S., Chen, C., Vermeulen, R. C. H., Wu, J., Lim, W., Chen, K., Chow, W., Ji, B., Chan, J. K. C., Chu, M., Li, Y., Yokota, J., Li, J., Chen, H., Xiang, Y., Yu, C., Kunitoh, H., Wu, G., Jin, L., Lo, Y., Shiraishi, K., Chen, Y., Lin, H., Wu, T., Wong, M. P., Wu, Y., Yang, P., Zhou, B., Shin, M., Fraumeni, J. F., Zheng, W., Lin, D., Chanock, S. J., Rothman, N., & Lan, Q.
- Affiliations
- National Cancer Institute (US)
- National Health Research Institutes (TW)
- Vanderbilt-Ingram Cancer Center (US)
- Aichi Cancer Center (JP)
- Seoul National University (KR)
- National University of Singapore (SG)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Albert Einstein College of Medicine (US)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Fudan University (CN)
- University of Utah (US)
- Kyungpook National University Medical Center (KR)
- Chonnam National University (KR)
- Nanjing Medical University (CN)
- Westat (United States) (US)
- Kindai University (JP)
- Taichung Veterans General Hospital (TW)
- Yale University (US)
- China National Environmental Monitoring Center (CN)
- China Medical University (CN)
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital, Guangdong Academy of Medical Sciences Guangzhou China
- Shanghai Jiao Tong University (CN)
- University of Hong Kong (HK)
- Anhui Medical University (CN)
- Kyungpook National University (KR)
- Korea University (KR)
- Shanghai Cancer Institute (CN)
- Chang Gung Memorial Hospital (TW)
- Huazhong University of Science and Technology (CN)
- Icahn School of Medicine at Mount Sinai (US)
- Guangdong General Hospital (CN)
- Kaohsiung Medical University (TW)
- Cancer Prevention Institute of California (US)
- National Cheng Kung University Hospital (TW)
- Korea University Anam Hospital (KR)
- The Catholic University of Korea Seoul St. Mary's Hospital (KR)
- Vanderbilt University Medical Center (US)
- Queen Mary Hospital (CN)
- Seoul National University Bundang Hospital (KR)
- Department of Oncology Wuhan Iron and Steel Corporation Staff Worker Hospital Wuhan China
- Taipei Veterans General Hospital (TW)
- National Cancer Center Research Institute (JP)
- Utrecht University (NL)
- Queen Elizabeth Hospital (CN)
- Institute of Predictive and Personalized Medicine of Cancer (ES)
- Qujing Center for Diseases Control and Prevention Sanjiangdadao Qujing China
- National Taiwan University Hospital (TW)
- Japanese Red Cross Medical Center (JP)
- Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences Fudan University Shanghai China
- National Taiwan University (TW)
- Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD
- Corresponding author
- Machiela, Mitchell J.
- ORCID
- Machiela, Mitchell J.
- Hsiung, Chao Agnes
- Shu, Xiao‐Ou
- Seow, Wei Jie
- Wang, Zhaoming
- Matsuo, Keitaro
- Hong, Yun‐Chul
- Seow, Adeline
- Wu, Chen
- Hosgood, H. Dean
- Chen, Kexin
- Wen, Wanqing
- Cawthon, Richard
- Chatterjee, Nilanjan
- Hu, Wei
- Caporaso, Neil E.
- Park, Jae Yong
- Chen, Chien‐Jen
- Kim, Yeul Hong
- Kim, Young Tae
- Landi, Maria Teresa
- Shen, Hongbing
- Lawrence, Charles
- Yeager, Meredith
- Chang, I‐Shou
- Mitsudomi, Tetsuya
- Kim, Hee Nam
- Chang, Gee‐Chen
- Bassig, Bryan A.
- Tucker, Margaret
- Yin, Zhihua
- Qian, Biyun
- Lee, Victor Ho Fun
- Lu, Daru
- Liu, Jianjun
- Hsiao, Chin‐Fu
- Sung, Jae Sook
- Kim, Jin Hee
- Gao, Yu‐Tang
- Guo, Huan
- Hu, Zhibin
- Hutchinson, Amy
- Wang, Wen‐Chang
- Klein, Robert J.
- Oh, In‐Jae
- Chen, Kuan‐Yu
- Berndt, Sonja I.
- Wu, Wei
- Chang, Jiang
- Zhang, Xu‐Chao
- Huang, Ming‐Shyan
- Wang, Junwen
- Zhao, Xueying
- Li, Yuqing
- Choi, Jin Eun
- Su, Wu‐Chou
- Park, Kyong Hwa
- Sung, Sook Whan
- Chen, Yuh‐Min
- Liu, Li
- Kang, Chang Hyun
- Hu, Lingmin
- Chen, Chung‐Hsing
- Pao, William
- Kim, Young‐Chul
- Yang, Tsung‐Ying
- Guan, Peng
- Tan, Wen
- Su, Jian
- Wang, Chih‐Liang
- Li, Haixin
- Sihoe, Alan Dart Loon
- Chen, Ying
- Hung, Jen‐Yu
- Kim, Jun Suk
- Cai, Qiuyin
- Lin, Chien‐Chung
- Park, In Kyu
- Xu, Ping
- Dong, Jing
- Kohno, Takashi
- Kweon, Sun‐Seog
- Vermeulen, Roel C.H
- Wu, Junjie
- Lim, Wei‐Yen
- Chen, Kun‐Chieh
- Chow, Wong‐Ho
- Ji, Bu‐Tian
- Chu, Minjie
- Yokota, Jun
- Li, Jihua
- Chen, Hongyan
- Xiang, Yong‐Bing
- Yu, Chong‐Jen
- Kunitoh, Hideo
- Wu, Guoping
- Shiraishi, Kouya
- Wu, Tangchun
- Wong, Maria Pik
- Wu, Yi‐Long
- Yang, Pan‐Chyr
- Zhou, Baosen
- Shin, Min‐Ho
- Zheng, Wei
- Lin, Dongxin
- Chanock, Stephen J.
- Rothman, Nathaniel
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2014-12-29
- Volume
- 137
- Issue
- 2
- Pages
- 311-319
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- PMC
- PMC4733320
- OpenAlex
- W1896451102
- Cited by
- 90
- References
- 31
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 9 · 2023: 10 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 10 · 2018: 10 · 2017: 9 · 2016: 16 · 2015: 5
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- onlinelibrary.wiley.com/termsAndConditions#vor (vor)
- Locations
- International Journal of Cancer (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- National University of Singapore (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- National Cancer Institute (HHSN261200800001E, N02 CP1101066)
- Ministry of Science and Technology of the People's Republic of China (2011BAI09B00)
- Government of Jiangsu Province (BE2010715)
- National Natural Science Foundation of China (81101549)
- National Science Council Taiwan (NSC 100-2319-B-400-001)
- U.S. Department of Health and Human Services (R01-CA121210, R37 CA70867)
- National Research Foundation of Korea (NRF-2014R1A2A2A05003665)
- China Medical Board (00726)
- Agency for Science, Technology and Research (A*STAR) of Singapore
- China National High-Tech Research and Development Program (2012AA02A517, 2012AA02A518, 2009AA022705)
- Chinese Lung Cancer Research Foundation
- Foundation of Guangdong Science and Technology Department (2006B60101010, 2007A032000002, 2011A030400010)
- General Research Fund of Research Grant Council, Hong Kong (781511M, 17121414M)
- Guangzhou Science and Information Technology Bureau (2011Y2-00014)
- Jiangsu Higher Education Institution
- Liaoning Provincial Department of Education (LS2010168)
- Ministry of Education, Science, Sports, Culture and Technology of Japan
- Ministry of Health (201002007)
- Ministry of Health & Welfare, Republic of Korea (0720550-2, A010250)
- Ministry of Health, Labor, and Welfare for Research on Applying Health Technology
- National Basic Research Program (2012CB944600)
- National Cancer Center Research and Development Fund
- National Foundation for Cancer Research
- National Key Basic Research and Development Program (2011CB503800)
- National Key Basic Research Program (2011CB503805)
- National Medical Research Council Singapore (NMRC/0897/2004, NMRC/1075/2006)
- National Nature Science Foundation of China (81102194)
- National Research Program for Biopharmaceuticals in Taiwan (DOH 100-TD-PB-111-TM013, MOST 103-2325-B-400-011)
- National Research Program on Genomic Medicine in Taiwan (DOH98-TD-G-111-015)
- National S&T Major Special Project (2011ZX09102-010-01)
- National Science Foundation of China (30890034, 91229105)
- Natural Science Foundation of Guangdong Province (S2011010000792)
- Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) (IRT1076)
- Tianjin Cancer Institute and Hospital
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- telomere length, lung cancer risk, never-smoking women, genetic variants, polygenic risk score, instrumental variables, telomerase reverse transcriptase, rs2736100, lung adenocarcinoma, squamous cell carcinoma, Shanghai Women's Health Study, Asian populations
- MeSH terms
- Adult, Aged, China, Female, Hong Kong, Humans, Japan, Lung Neoplasms, Middle Aged, Prospective Studies, Risk Factors, Singapore, Smoking, Taiwan, Odds Ratio, Telomere, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Asian People, Genome-Wide Association Study, Republic of Korea, Telomere Homeostasis
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