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

Hanla A Park ORCID logo; Sonja Neumeyer; Kyriaki Michailidou; Manjeet K Bolla; Qin Wang; Joe Dennis ORCID logo; Thomas U Ahearn; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; +143 more... Volker Arndt; Kristan J Aronson; Annelie Augustinsson ORCID logo; Adinda Baten; Laura E Beane Freeman; Heiko Becher; Matthias W Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Natalia V Bogdanova; Stig E Bojesen; Hiltrud Brauch; Hermann Brenner ORCID logo; Sara Y Brucker; Barbara Burwinkel; Daniele Campa; Federico Canzian ORCID logo; Jose E Castelao; Stephen J Chanock; Georgia Chenevix-Trench; Christine L Clarke; NBCS Collaborators; Don M Conroy; Fergus J Couch; Angela Cox ORCID logo; Simon S Cross; Kamila Czene; Mary B Daly; Peter Devilee ORCID logo; Thilo Dörk; Isabel Dos-Santos-Silva ORCID logo; Miriam Dwek; Diana M Eccles; A Heather Eliassen; Christoph Engel; Mikael Eriksson; D Gareth Evans; Peter A Fasching ORCID logo; Henrik Flyger; Lin Fritschi; Montserrat García-Closas; José A 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 ORCID logo; Steven N Hart ORCID logo; Wei He; Bernadette AM Heemskerk-Gerritsen ORCID logo; John L Hopper; David J Hunter; ABCTB Investigators; kConFab Investigators; Agnes Jager; Anna Jakubowska ORCID logo; Esther M John; Audrey Jung; Rudolf Kaaks; Pooja Middha Kapoor ORCID logo; Renske Keeman; Elza Khusnutdinova; Cari M Kitahara; Linetta B Koppert; Stella Koutros; Vessela N Kristensen; Allison W Kurian ORCID logo; James Lacey; Diether Lambrechts; Loic Le Marchand; Wing-Yee Lo; Jan Lubiński; Arto Mannermaa; Mehdi Manoochehri; Sara Margolin; Maria Elena Martinez; Dimitrios Mavroudis; Alfons Meindl; Usha Menon; Roger L Milne; Taru A Muranen; Heli Nevanlinna; William G Newman ORCID logo; Børge G Nordestgaard; Kenneth Offit; Andrew F Olshan; Håkan Olsson; Tjoung-Won Park-Simon; Paolo Peterlongo ORCID logo; Julian Peto ORCID logo; Dijana Plaseska-Karanfilska; Nadege Presneau; Paolo Radice; Gad Rennert; Hedy S Rennert; Atocha Romero; Emmanouil Saloustros; Elinor J Sawyer ORCID logo; Marjanka K Schmidt; Rita K Schmutzler; Minouk J Schoemaker; Lukas Schwentner; Christopher Scott ORCID logo; Mitul Shah; Xiao-Ou Shu; Jacques Simard; Ann Smeets ORCID logo; Melissa C Southey; John J Spinelli; Victoria Stevens; Anthony J Swerdlow; Rulla M Tamimi; William J Tapper; Jack A Taylor; Mary Beth Terry; Ian Tomlinson ORCID logo; Melissa A Troester; Thérèse Truong ORCID logo; Celine M Vachon; Elke M van Veen; Joseph Vijai; Sophia Wang; Camilla Wendt; Robert Winqvist; Alicja Wolk; Argyrios Ziogas; Alison M Dunning; Paul DP Pharoah ORCID logo; Douglas F Easton; Wei Zheng; Peter Kraft; Jenny Chang-Claude; NBCS Collaborators, ABCTB Investigators, kConFab Investigators; (2021) Mendelian randomisation study of smoking exposure in relation to breast cancer risk. British journal of cancer, 125 (8). pp. 1135-1145. ISSN 0007-0920 DOI: 10.1038/s41416-021-01432-8
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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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