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Cyp2a6 activity and...
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Du, MulongDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China
(author)
Cyp2a6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility
- Article/chapterEnglish2024
Publisher, publication year, extent ...
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American Association For Cancer Research (AACR),2024
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-222228
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222228URI
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https://doi.org/10.1158/0008-5472.CAN-23-0900DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen–metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke–exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85–0.91, P = 2.18 X 10-16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Xin, JunyiDepartment of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Jiangsu, Nanjing, China
(author)
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Zheng, RuiDepart-ment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China
(author)
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Yuan, QianyuDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States
(author)
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Wang, ZhihuiDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States
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Liu, HongliangDuke Cancer Institute, Duke University Medical Center, NC, Durham, United States; Department of Population Health Sciences, Duke University School of Medicine, NC, Durham, United States
(author)
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Liu, HantingDepart-ment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China
(author)
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Cai, GuoshuaiDepartment of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, SC, Columbia, United States
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Albanes, DemetriusDivision of Cancer Epidemiology and Genetics, NCI, US NIH, MD, Bethesda, United States
(author)
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Lam, StephenBritish Columbia Cancer Agency, BC, Vancouver, Canada
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Tardon, AdoninaFaculty of Medicine, University of Oviedo, ISPA and CIBERESP, Oviedo, Spain
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Chen, ChuProgram in Epidemiology, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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Bojesen, Stig E.Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark
(author)
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Landi, Maria TeresaDivision of Cancer-Epidemiology and Genetics, NCI, US NIH, MD, Bethesda, United States
(author)
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Johansson, MattiasInternational Agency for Research on Cancer, World-Health Organization, Lyon, France
(author)
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Risch, AngelaUniversity of Salzburg and Cancer Cluster Salzburg, Salzburg, Austria; Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany; German Center for Lung Research (DZL), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
(author)
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Bickeboller, HeikeDepartment of Genetic Epidemiology, University Medical Center, Georg August University Gottingen, Gottingen, Germany
(author)
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Wichmann, H-ErichInstitute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany; Institute of Epidemiology II, Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Statistics and Epidemiology, Technical University of Munich, Munich, Germany
(author)
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Rennert, GadClalit National Cancer Control Center, Carmel Medical Center, Technion Faculty of Medicine, Haifa, Israel
(author)
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Arnold, SusanneMarkey Cancer Center, University of Kentucky, KY, Lexington, United States
(author)
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Brennan, PaulInternational Agency for Research on Cancer, World Health Organization, Lyon, France
(author)
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Field, John K.Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
(author)
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Shete, Sanjay S.Department of Epidemiology, Division of Cancer Prevention and Population Science, The University of Texas, MD Anderson Cancer Center, TX, Houston, United States
(author)
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Le Marchand, LoïcEpidemiology Program, University of Hawaii Cancer Center, Hawaii, Honolulu, United States
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Liu, GeoffreyPrincess Margaret Cancer Center, University of Toronto, ON, Toronto, Canada
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Andrew, Angeline S.Norris Cotton Cancer Center, Geisel School of Medicine, NH, Hanover, United States
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Kiemeney, Lambertus A.Radboud University Medical Center, Nijmegen, Netherlands
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Zienolddiny, ShanNational Institute of Occupational Health, Oslo, Norway
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Grankvist, KjellUmeå universitet,Institutionen för medicinsk biovetenskap(Swepub:umu)kjgr0002
(author)
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Johansson, MikaelUmeå universitet,Onkologi,Department of Radiation Sciences, Umeå, Sweden(Swepub:umu)mijo0025
(author)
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Caporaso, Neil E.Division of Cancer Epidemiology and Genetics, NCI, US-NIH, MD, Bethesda, United States
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Cox, AngelaDepartment of Oncology, University of Sheffield, Sheffield, United Kingdom
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Hong, Yun-ChulDepartment of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
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Yuan, Jian-MinUPMC Hillman Cancer Center, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA, Pittsburgh, United States
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Schabath, Matthew B.Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States
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Aldrich, Melinda C.Department of Medicine, Vanderbilt University Medical Center, TN, Nashville, United States
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Wang, MeilinDepart-ment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China
(author)
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Shen, HongbingDepartment 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, Jiangsu, Nanjing, China
(author)
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Chen, FengDepartment of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China
(author)
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Zhang, ZhengdongDepart-ment of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China
(author)
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Hung, Rayjean J.Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, University of Toronto, ON, Toronto, Canada
(author)
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Amos, Christopher I.Institute for Clinical and Translational Research, Baylor Medical College, TX, Houston, United States
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Wei, QingyiDuke Cancer Institute, Duke University Medical Center, NC, Durham, United States; Department of Population Health Sciences, Duke University School of Medicine, NC, Durham, United States
(author)
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Lazarus, PhilipDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, WA, Spokane, United States
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Christiani, David C.Department of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Medicine, Massachusetts General Hospital, MA, Boston, United States
(author)
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Department of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, ChinaDepartment of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Jiangsu, Nanjing, China
(creator_code:org_t)
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In:Cancer Research: American Association For Cancer Research (AACR)84:4, s. 616-6250008-54721538-7445
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Du, Mulong
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Xin, Junyi
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Zheng, Rui
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Yuan, Qianyu
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Wang, Zhihui
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Liu, Hongliang
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Liu, Hanting
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Cai, Guoshuai
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Albanes, Demetri ...
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Lam, Stephen
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Tardon, Adonina
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Chen, Chu
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Bojesen, Stig E.
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Landi, Maria Ter ...
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Johansson, Matti ...
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Risch, Angela
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Bickeboller, Hei ...
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Wichmann, H-Eric ...
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Rennert, Gad
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Arnold, Susanne
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Brennan, Paul
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Field, John K.
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Shete, Sanjay S.
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Le Marchand, Loï ...
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Liu, Geoffrey
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Andrew, Angeline ...
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Kiemeney, Lamber ...
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Zienolddiny, Sha ...
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Grankvist, Kjell
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Johansson, Mikae ...
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Caporaso, Neil E ...
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Cox, Angela
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Hong, Yun-Chul
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Yuan, Jian-Min
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Schabath, Matthe ...
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Aldrich, Melinda ...
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Wang, Meilin
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Shen, Hongbing
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Chen, Feng
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Zhang, Zhengdong
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