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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 , 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 , 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 , 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
Mendelian randomisation study of smoking exposure in relation to breast cancer risk
Br J Cancer. 2021 Aug 2
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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.
Notes
1532-1827 Park, Hanla A Orcid: 0000-0001-8055-3729 Neumeyer, Sonja Michailidou, Kyriaki Bolla, Manjeet K Wang, Qin Dennis, Joe Orcid: 0000-0003-4591-1214 Ahearn, Thomas U Andrulis, Irene L Anton-Culver, Hoda Antonenkova, Natalia N Arndt, Volker Aronson, Kristan J Augustinsson, Annelie Orcid: 0000-0003-3415-0536 Baten, Adinda Beane Freeman, Laura E Becher, Heiko Beckmann, Matthias W Behrens, Sabine Benitez, Javier Bermisheva, Marina Bogdanova, Natalia V Bojesen, Stig E Brauch, Hiltrud Brenner, Hermann Orcid: 0000-0002-6129-1572 Brucker, Sara Y Burwinkel, Barbara Campa, Daniele Canzian, Federico Orcid: 0000-0002-4261-4583 Castelao, Jose E Chanock, Stephen J Chenevix-Trench, Georgia Clarke, Christine L NBCS Collaborators Conroy, Don M Couch, Fergus J Cox, Angela Orcid: 0000-0002-5138-1099 Cross, Simon S Czene, Kamila Daly, Mary B Devilee, Peter Orcid: 0000-0002-8023-2009 Dörk, Thilo Dos-Santos-Silva, Isabel Dwek, Miriam Eccles, Diana M Eliassen, A Heather Engel, Christoph Eriksson, Mikael Evans, D Gareth Fasching, Peter A Orcid: 0000-0003-4885-8471 Flyger, Henrik Fritschi, Lin García-Closas, Montserrat García-Sáenz, José A Gaudet, Mia M Giles, Graham G Glendon, Gord Goldberg, Mark S Goldgar, David E González-Neira, Anna Grip, Mervi Guénel, Pascal Hahnen, Eric Haiman, Christopher A Håkansson, Niclas Hall, Per Hamann, Ute Han, Sileny Harkness, Elaine F Orcid: 0000-0001-6625-7739 Hart, Steven N Orcid: 0000-0001-7714-2734 He, Wei Heemskerk-Gerritsen, Bernadette A M Orcid: 0000-0002-9724-6693 Hopper, John L Hunter, David J ABCTB Investigators kConFab Investigators Jager, Agnes Jakubowska, Anna Orcid: 0000-0002-5650-0501 John, Esther M Jung, Audrey Kaaks, Rudolf Kapoor, Pooja Middha Orcid: 0000-0001-5503-8215 Keeman, Renske Khusnutdinova, Elza Kitahara, Cari M Koppert, Linetta B Koutros, Stella Kristensen, Vessela N Kurian, Allison W Orcid: 0000-0002-6175-9470 Lacey, James Lambrechts, Diether Le Marchand, Loic Lo, Wing-Yee Lubiński, Jan Mannermaa, Arto Manoochehri, Mehdi Margolin, Sara Martinez, Maria Elena Mavroudis, Dimitrios Meindl, Alfons Menon, Usha Milne, Roger L Muranen, Taru A Nevanlinna, Heli Newman, William G Orcid: 0000-0002-6382-4678 Nordestgaard, Børge G Offit, Kenneth Olshan, Andrew F Olsson, Håkan Park-Simon, Tjoung-Won Peterlongo, Paolo Orcid: 0000-0001-6951-6855 Peto, Julian Orcid: 0000-0002-1685-8912 Plaseska-Karanfilska, Dijana Presneau, Nadege Radice, Paolo Rennert, Gad Rennert, Hedy S Romero, Atocha Saloustros, Emmanouil Sawyer, Elinor J Orcid: 0000-0001-8285-4111 Schmidt, Marjanka K Schmutzler, Rita K Schoemaker, Minouk J Schwentner, Lukas Scott, Christopher Orcid: 0000-0003-1340-0647 Shah, Mitul Shu, Xiao-Ou Simard, Jacques Smeets, Ann Orcid: 0000-0002-5091-6602 Southey, Melissa C Spinelli, John J Stevens, Victoria Swerdlow, Anthony J Tamimi, Rulla M Tapper, William J Taylor, Jack A Terry, Mary Beth Tomlinson, Ian Orcid: 0000-0003-3037-1470 Troester, Melissa A Truong, Thérèse Orcid: 0000-0002-2943-6786 Vachon, Celine M van Veen, Elke M Vijai, Joseph Wang, Sophia Wendt, Camilla Winqvist, Robert Wolk, Alicja Ziogas, Argyrios Dunning, Alison M Pharoah, Paul D P Orcid: 0000-0001-8494-732x Easton, Douglas F Zheng, Wei Kraft, Peter Chang-Claude, Jenny Journal Article England Br J Cancer. 2021 Aug 2. doi: 10.1038/s41416-021-01432-8.