Cyp2a6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility

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Cyp2a6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility

Du, Mulong (author): 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, China

Xin, Junyi (author): Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Jiangsu, Nanjing, China

Zheng, Rui (author): Depart-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

Yuan, Qianyu (author): Department of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States

Wang, Zhihui (author): Department of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States

Liu, Hongliang (author): Duke Cancer Institute, Duke University Medical Center, NC, Durham, United States; Department of Population Health Sciences, Duke University School of Medicine, NC, Durham, United States

Liu, Hanting (author): Depart-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

Cai, Guoshuai (author): Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, SC, Columbia, United States

Albanes, Demetrius (author): Division of Cancer Epidemiology and Genetics, NCI, US NIH, MD, Bethesda, United States

Lam, Stephen (author): British Columbia Cancer Agency, BC, Vancouver, Canada

Tardon, Adonina (author): Faculty of Medicine, University of Oviedo, ISPA and CIBERESP, Oviedo, Spain

Chen, Chu (author): Program in Epidemiology, Fred Hutchinson Cancer Research Center, WA, Seattle, United States

Bojesen, Stig E. (author): 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

Landi, Maria Teresa (author): Division of Cancer-Epidemiology and Genetics, NCI, US NIH, MD, Bethesda, United States

Johansson, Mattias (author): International Agency for Research on Cancer, World-Health Organization, Lyon, France

Risch, Angela (author): University 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

Bickeboller, Heike (author): Department of Genetic Epidemiology, University Medical Center, Georg August University Gottingen, Gottingen, Germany

Wichmann, H-Erich (author): Institute 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

Rennert, Gad (author): Clalit National Cancer Control Center, Carmel Medical Center, Technion Faculty of Medicine, Haifa, Israel

Arnold, Susanne (author): Markey Cancer Center, University of Kentucky, KY, Lexington, United States

Brennan, Paul (author): International Agency for Research on Cancer, World Health Organization, Lyon, France

Field, John K. (author): Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom

Shete, Sanjay S. (author): Department of Epidemiology, Division of Cancer Prevention and Population Science, The University of Texas, MD Anderson Cancer Center, TX, Houston, United States

Le Marchand, Loïc (author): Epidemiology Program, University of Hawaii Cancer Center, Hawaii, Honolulu, United States

Liu, Geoffrey (author): Princess Margaret Cancer Center, University of Toronto, ON, Toronto, Canada

Andrew, Angeline S. (author): Norris Cotton Cancer Center, Geisel School of Medicine, NH, Hanover, United States

Kiemeney, Lambertus A. (author): Radboud University Medical Center, Nijmegen, Netherlands

Zienolddiny, Shan (author): National Institute of Occupational Health, Oslo, Norway

Grankvist, Kjell (author): Umeå universitet,Institutionen för medicinsk biovetenskap

Johansson, Mikael (author): Umeå universitet,Onkologi,Department of Radiation Sciences, Umeå, Sweden

Caporaso, Neil E. (author): Division of Cancer Epidemiology and Genetics, NCI, US-NIH, MD, Bethesda, United States

Cox, Angela (author): Department of Oncology, University of Sheffield, Sheffield, United Kingdom

Hong, Yun-Chul (author): Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea

Yuan, Jian-Min (author): UPMC Hillman Cancer Center, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA, Pittsburgh, United States

Schabath, Matthew B. (author): Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States

Aldrich, Melinda C. (author): Department of Medicine, Vanderbilt University Medical Center, TN, Nashville, United States

Wang, Meilin (author): Depart-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

Shen, Hongbing (author): 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, Jiangsu, Nanjing, China

Chen, Feng (author): Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Jiangsu, Nanjing, China

Zhang, Zhengdong (author): Depart-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

Hung, Rayjean J. (author): Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, University of Toronto, ON, Toronto, Canada

Amos, Christopher I. (author): Institute for Clinical and Translational Research, Baylor Medical College, TX, Houston, United States

Wei, Qingyi (author): Duke Cancer Institute, Duke University Medical Center, NC, Durham, United States; Department of Population Health Sciences, Duke University School of Medicine, NC, Durham, United States

Lazarus, Philip (author): Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, WA, Spokane, United States

Christiani, David C. (author): 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

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Department of Environmental Health, Harvard TH. 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 Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Jiangsu, Nanjing, China (creator_code:org_t)

American Association For Cancer Research (AACR), 2024
2024
English.
In: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 84:4, s. 616-625

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

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By the author/editor: Du, Mulong; Xin, Junyi; Zheng, Rui; Yuan, Qianyu; Wang, Zhihui; Liu, Hongliang; show more...; Liu, Hanting; Cai, Guoshuai; Albanes, Demetri ...; Lam, Stephen; Tardon, Adonina; Chen, Chu; Bojesen, Stig E.; Landi, Maria Ter ...; Johansson, Matti ...; Risch, Angela; Bickeboller, Hei ...; Wichmann, H-Eric ...; Rennert, Gad; Arnold, Susanne; Brennan, Paul; Field, John K.; Shete, Sanjay S.; Le Marchand, Loï ...; Liu, Geoffrey; Andrew, Angeline ...; Kiemeney, Lamber ...; Zienolddiny, Sha ...; Grankvist, Kjell; Johansson, Mikae ...; Caporaso, Neil E ...; Cox, Angela; Hong, Yun-Chul; Yuan, Jian-Min; Schabath, Matthe ...; Aldrich, Melinda ...; Wang, Meilin; Shen, Hongbing; Chen, Feng; Zhang, Zhengdong; Hung, Rayjean J.; Amos, Christophe ...; Wei, Qingyi; Lazarus, Philip; Christiani, Davi ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

Articles in the publication: Cancer Research

By the university: Umeå University

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Cyp2a6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility

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