Mendelian randomisation study of smoking exposure in relation to breast cancer risk
Hanla A. Park, Sonja Neumeyer, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Joe Dennis, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton‐Culver, Natalia Antonenkova, Volker Arndt, Kristan J. Aronson, Annelie Augustinsson, Adinda Baten, Laura E. Beane Freeman, Heiko Becher, Matthias W. Beckmann, Sabine Behrens, Javier Benı́tez, Marina Bermisheva, Natalia Bogdanova, Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Sara Y. Brucker, Barbara Burwinkel, Daniele Campa, Federico Canzian, Jose E. Castelao, Stephen J. Chanock, Georgia Chenevix‐Trench, Christine L. Clarke, NBCS Collaborators, Anne‐Lise Børresen‐Dale, Grethe I.G. Alnæs, Kristine Kleivi Sahlberg, Lars Ottestad, Rolf Kåresen, Ellen Schlichting, Marit Muri Holmen, Toril Sauer, Vilde Drageset Haakensen, Olav Engebråten, Bjørn Naume, Alexander Fosså, Cecile E. Kiserud, Kristin V. Reinertsen, Åslaug Helland, Margit Riis, Jürgen Geisler, Don Conroy, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Isabel dos‐Santos‐Silva, Miriam Dwek, Diana M. Eccles, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Henrik Flyger, Lin Fritschi, Montserrat García‐Closas, José Á. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Gord Glendon, Mark S. Goldberg, David E. Goldgar, Anna González‐Neira, Mervi Grip, Pascal Guénel, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Sileny Han, Elaine F. Harkness, Steven N. Hart, Wei He, Bernadette A. M. Heemskerk‐Gerritsen, John L. Hopper, David J. Hunter, ABCTB Investigators, Christine L. Clarke, Deborah J. Marsh, Rodney J. Scott, Robert C. Baxter, Desmond Yip, Jane Carpenter, Alison Davis, Nirmala Pathmanathan, Peter T. Simpson
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: ), 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.