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Identification of genetically predicted DNA methylation markers associated with non–small cell lung cancer risk among 34,964 cases and 448,579 controls

Zhao, Xiaoyu (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Statistics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Yang, Meiqi (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Fan, Jingyi (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China; Health Management Center, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China
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Wang, Mei (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Wang, Yifan (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Qin, Na (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China
Zhu, Meng (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China; Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
Jiang, Yue (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China
Gorlova, Olga Y. (författare)
Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, NH, Lebanon, United States; Department of Medicine, Epidemiology Section, Institute for Clinical and Translational Research, Baylor Medical College, TX, Houston, United States
Gorlov, Ivan P. (författare)
Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, NH, Lebanon, United States; Department of Medicine, Epidemiology Section, Institute for Clinical and Translational Research, Baylor Medical College, TX, Houston, United States
Albanes, Demetrius (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Bethesda, United States
Lam, Stephen (författare)
Department of Integrative Oncology, British Columbia Cancer Agency, BC, Vancouver, Canada
Tardón, Adonina (författare)
Department of Public Health IUOPA, University of Oviedo, ISPA and CIBERESP, Oviedo, Spain
Chen, Chu (författare)
Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Goodman, Gary E. (författare)
Public Health Sciences Division, Swedish Cancer Institute, WA, Seattle, United States
Bojesen, Stig E. (författare)
Department of Clinical Biochemistry, Copenhagen University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Landi, Maria Teresa (författare)
National Cancer Institute, MD, Bethesda, United States
Johansson, Mattias (författare)
Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
Risch, Angela (författare)
Department of Biosciences, Allergy-Cancer-BioNano Research Centre, University of Salzburg, Salzburg, Austria; Division of Epigenomics and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg, Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC-H), German Center for Lung Research (DZL), Heidelberg, Germany
Wichmann, H.-Erich (författare)
Institute of Epidemiology, Helmholtz Center Munich, Neuherberg, Germany
Bickeböller, Heike (författare)
Department of Genetic Epidemiology, University Medical Center Goettingen, Goettingen, Germany
Christiani, David C. (författare)
Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States
Rennert, Gad (författare)
Technion Faculty of Medicine, Carmel Medical Center, Haifa, Israel
Arnold, Susanne M. (författare)
Markey Cancer Center, University of Kentucky, KY, Lexington, United States
Brennan, Paul (författare)
Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
Field, John K. (författare)
Molecular and Clinical Cancer Medicine, Roy Castle Lung Cancer Research Programme, The University of Liverpool Institute of Translational Medicine, Liverpool, United Kingdom
Shete, Sanjay (författare)
Department of Epidemiology, The University of Texas, MD Anderson Cancer Center, TX, Houston, United States
Le Marchand, Loïc (författare)
Epidemiology Program, University of Hawai'i Cancer Center, HI, Honolulu, United States
Liu, Geoffrey (författare)
Princess Margaret Cancer Centre, ON, Toronto, Canada
Hung, Rayjean J. (författare)
Prosseman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, ON, Toronto, Canada
Andrew, Angeline S. (författare)
Department of Neurology, Dartmouth-Hitchcock Medical Center, NH, Lebanon, United States
Kiemeney, Lambertus A. (författare)
Department for Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands
Zienolddiny, Shanbeh (författare)
National Institute of Occupational Health (STAMI), Oslo, Norway
Grankvist, Kjell (författare)
Umeå universitet,Klinisk kemi
Johansson, Mikael (författare)
Umeå universitet,Institutionen för strålningsvetenskaper
Caporaso, Neil E. (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, Rockville, United States
Woll, Penella J. (författare)
Academic Unit of Clinical Oncology, University of Sheffield, Sheffield, United Kingdom
Lazarus, Philip (författare)
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, WA, Spokane, United States
Schabath, Matthew B. (författare)
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States
Aldrich, Melinda C. (författare)
Department of Medicine (Division of Genetic Medicine), Vanderbilt University Medical Center, TN, Nashville, United States
Patel, Alpa V. (författare)
Behavioral and Epidemiology Research Group, American Cancer Society, GA, Atlanta, United States
Davies, Michael P. A. (författare)
Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Ma, Hongxia (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China
Jin, Guangfu (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China
Hu, Zhibin (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China
Amos, Christopher I. (författare)
Baylor College of Medicine, Institute for Clinical and Translational Research, TX, Houston, United States
Shen, Hongbing (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China
Dai, Juncheng (författare)
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Gusu School, Nanjing Medical University, Nanjing, China
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 (creator_code:org_t)
John Wiley & Sons, 2024
2024
Engelska.
Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 130:6, s. 913-926
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non–small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated.Methods: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways.Results: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10−6) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10−3), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified.Conclusions: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby.Plain Language Summary: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non–small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

association study
DNA methylation
gene expression
genetic prediction
non–small cell lung cancer risk

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