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Mendelian randomisation study of smoking exposure in relation to breast cancer risk.

About this Publication
Title
Mendelian randomisation study of smoking exposure in relation to breast cancer risk.
Pubmed ID
34341517 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Br J Cancer. 2021 Oct; Volume 125 (Issue 8): Pages 1135-1145
Authors
Park HA, Neumeyer S, Michailidou K, Bolla MK, Wang Q, Dennis J, Ahearn TU, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Aronson KJ, Augustinsson A, Baten A, Beane Freeman LE, Becher H, Beckmann MW, Behrens S, Benitez J, Bermisheva M, ...show more Bogdanova NV, Bojesen SE, Brauch H, Brenner H, Brucker SY, Burwinkel B, Campa D, Canzian F, Castelao JE, Chanock SJ, Chenevix-Trench G, Clarke CL, NBCS Collaborators, Conroy DM, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, Devilee P, Dörk T, Dos-Santos-Silva I, Dwek M, Eccles DM, Eliassen AH, Engel C, Eriksson M, Evans DG, Fasching PA, Flyger H, Fritschi L, García-Closas M, García-Sáenz JA, Gaudet MM, Giles GG, Glendon G, Goldberg MS, Goldgar DE, González-Neira A, Grip M, Guénel P, Hahnen E, Haiman CA, Håkansson N, Hall P, Hamann U, Han S, Harkness EF, Hart SN, He W, Heemskerk-Gerritsen BAM, Hopper JL, Hunter DJ, ABCTB Investigators, kConFab Investigators, Jager A, Jakubowska A, John EM, Jung A, Kaaks R, Kapoor PM, Keeman R, Khusnutdinova E, Kitahara CM, Koppert LB, Koutros S, Kristensen VN, Kurian AW, Lacey J, Lambrechts D, Le Marchand L, Lo WY, Lubiński J, Mannermaa A, Manoochehri M, Margolin S, Martinez ME, Mavroudis D, Meindl A, Menon U, Milne RL, Muranen TA, Nevanlinna H, Newman WG, Nordestgaard BG, Offit K, Olshan AF, Olsson H, Park-Simon TW, Peterlongo P, Peto J, Plaseska-Karanfilska D, Presneau N, Radice P, Rennert G, Rennert HS, Romero A, Saloustros E, Sawyer EJ, Schmidt MK, Schmutzler RK, Schoemaker MJ, Schwentner L, Scott C, Shah M, Shu XO, Simard J, Smeets A, Southey MC, Spinelli JJ, Stevens V, Swerdlow AJ, Tamimi RM, Tapper WJ, Taylor JA, Terry MB, Tomlinson I, Troester MA, Truong T, Vachon CM, van Veen EM, Vijai J, Wang S, Wendt C, Winqvist R, Wolk A, Ziogas A, Dunning AM, Pharoah PDP, Easton DF, Zheng W, Kraft P, Chang-Claude J
Affiliations
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Biostatistics Unit, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
  • Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
  • Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
  • Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.
  • N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Public Health Sciences, and Cancer Research Institute, Queen's University, Kingston, ON, Canada.
  • Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
...show more
  • Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
  • Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
  • Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
  • Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
  • Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
  • Department of Gynecology and Obstetrics, University of Tübingen, Tübingen, Germany.
  • Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain.
  • Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia.
  • Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
  • Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
  • Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
  • School of Life Sciences, University of Westminster, London, UK.
  • Faculty of Medicine, University of Southampton, Southampton, UK.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
  • Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
  • Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • School of Public Health, Curtin University, Perth, WA, Australia.
  • Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
  • Department of Medicine, McGill University, Montréal, QC, Canada.
  • Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.
  • Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
  • Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
  • Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
  • Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
  • Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Department of Surgical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
  • Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
  • Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA.
  • VIB Center for Cancer Biology, Leuven, Belgium.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
  • Department of Oncology, Södersjukhuset, Stockholm, Sweden.
  • Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
  • Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.
  • Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich, Germany.
  • MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, London, UK.
  • Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Genome Diagnostics Program, IFOM - the FIRC Institute of Molecular Oncology, Milan, Italy.
  • Research Centre for Genetic Engineering and Biotechnology 'Georgi D, Efremov', MASA, Skopje, Republic of North Macedonia.
  • Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
  • Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel.
  • Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
  • Department of Oncology, University Hospital of Larissa, Larissa, Greece.
  • School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London, UK.
  • Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
  • Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Genomics Center, Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Québec City, QC, Canada.
  • Department of Surgical Oncology, University Hospitals Leuven, Leuven, Belgium.
  • Population Oncology, BC Cancer, Vancouver, BC, Canada.
  • Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
  • Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
  • Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
  • Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
  • Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
  • Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. j.chang-claude@dkfz.de.
Abstract

BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.

METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.

RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.

CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

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