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

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, Freeman LEB, Becher H, Beckmann M, Behrens S, Benitez J, Bermisheva M, Bogdanova N, Bojesen SE, Brauch H, Brenner H, Brucker SY, Burwinkel B, Campa D, Canzian F, Castelao JE, Chanock SJ, Chenevix-Trench G, Clarke CL, Conroy DM, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, Devilee P, Dork T, Dos-Santos-Silva I, Dwek M, Eccles DM, Eliassen AH, Engel C, Eriksson M, Evans DG, Fasching P, Flyger H, Fritschi L, Garcia-Closas M, Garcia-Saenz JA, Gaudet MM, Giles GG, Glendon G, Goldberg MS, Goldgar DE, Gonzalez-Neira A, Grip M, Guenel P, Hahnen E, Haiman CA, Hakansson N, Hall P, Hamann U, Han S, Harkness EF, Hart SN, He W, Heemskerk-Gerritsen BAM, Hopper JL, Hunter DJ, 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, Lemarchand L, Lo WY, Mannermaa A, Manoochehri M, Margolin S, Elenamartinez M, 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 (2021)

Publication Type: Journal article

Publication year: 2021

Journal

DOI: 10.1038/s41416-021-01432-8

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 x 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.

Authors with CRIS profile

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI / NKI-AVL) Netherlands (NL) National Cancer Institute (NCI) United States (USA) (US) University of Southampton United Kingdom (GB) Cyprus Institute of Neurology and Genetics Cyprus (CY) University of Cambridge United Kingdom (GB) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Queen's University United Kingdom (GB) Lund University / Lunds universitet Sweden (SE) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) Russian Federation (RU) Copenhagen University Hospital Denmark (DK) Robert-Bosch-Krankenhaus Germany (DE) Servizo Galego de Saúde Spain (ES) University of Sydney (USYD) Australia (AU) Mayo Clinic United States (USA) (US) University of Sheffield United Kingdom (GB) Fox Chase Cancer Center United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) University of Westminster United Kingdom (GB) Karolinska Institute Sweden (SE) Cancer Council Victoria Australia (AU) Mount Sinai Hospital (MSH) Canada (CA) McGill University Canada (CA) Universität zu Köln Germany (DE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) University of Manchester United Kingdom (GB) Harvard University United States (USA) (US) University of California Irvine United States (USA) (US) Leiden University Medical Center Netherlands (NL) London School of Hygiene and Tropical Medicine United Kingdom (GB) Universität Leipzig Germany (DE) Centro de Investigación Biomédica en Red (CIBER) Spain (ES) University of Utah United States (USA) (US) Oulun Yliopisto / University of Oulo Finland (FI) University of Paris 11 - Paris-Sud / Université Paris XI Paris-Sud France (FR) The University of Melbourne Australia (AU) University of Hawaii (U.H.) United States (USA) (US) Universitätsklinikum Ulm Germany (DE) City of Hope Medical Center United States (USA) (US) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University of Eastern Finland Finland (FI) Södersjukhuset Sweden (SE) University General Hospital of Heraklion Greece (GR) Helsingin yliopisto / University of Helsinki Finland (FI) University of North Carolina at Chapel Hill United States (USA) (US) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Carmel Medical Center Israel (IL) Hospital Universitario Puerta de Hierro - Majadahonda Spain (ES) King’s College London United Kingdom (GB) The Institute of Cancer Research (ICR) United Kingdom (GB) BC Cancer Canada (CA) American Cancer Society United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Columbia University United States (USA) (US) University of Birmingham United Kingdom (GB) Memorial Sloan Kettering Cancer Center United States (USA) (US) Vanderbilt University United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Ciber de Enfermedades Raras (CIBERER) Spain (ES) Eberhard Karls Universität Tübingen Germany (DE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Curtin University Australia (AU) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of Southern California (USC) United States (USA) (US) Erasmus University Medical Center (MC) Netherlands (NL) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Stanford University United States (USA) (US) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) Ludwig-Maximilians-Universität (LMU) Germany (DE) University College London (UCL) United Kingdom (GB) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) General University Hospital of Larissa Greece (GR) Université Laval (UL) Canada (CA) National Institute of Environmental Health Sciences (NIEHS) United States (USA) (US)

How to cite

APA:

Park, H.A., Neumeyer, S., Michailidou, K., Bolla, M.K., Wang, Q., Dennis, J.,... Chang-Claude, J. (2021). Mendelian randomisation study of smoking exposure in relation to breast cancer risk. British Journal of Cancer. https://doi.org/10.1038/s41416-021-01432-8

MLA:

Park, Hanla A., et al. "Mendelian randomisation study of smoking exposure in relation to breast cancer risk." British Journal of Cancer (2021).

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