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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, 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, 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, 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, Deborah J. Marsh, Rodney J. Scott, Robert C. Baxter, Desmond Yip, Jane Carpenter, Alison Davis, Nirmala Pathmanathan, Peter T. Simpson, J. Dinny Graham, Mythily Sachchithananthan, David J. Amor, Lesley Andrews, Yoland Antill, Rosemary L. Balleine, Jonathan Beesley, Ian Bennett, Michael Bogwitz, Leon Botes, Meagan Brennan, Melissa A. Brown, Michael F. Buckley, Jo Burke, Phyllis Butow, Liz Caldon, Ian Campbell, Deepa Chauhan, Manisha Chauhan, Alice Christian, Paul A. Cohen, Alison Colley, Ashley Crook, James Cui, Margaret C. Cummings, Sarah‐Jane Dawson, Anna DeFazio, Martin B. Delatycki, Rebecca Dickson, Joanne Dixon, Ted Edkins, Stacey L. Edwards, Gelareh Farshid, Andrew Fellows, Georgina Fenton, Michael Field, James M. Flanagan, Peter C.C. Fong, Laura Forrest, Stephen B. Fox, Juliet D. French, Michael Friedländer, Clara Gaff, Mike Gattas, Peter George, Sian Greening, Marion Harris, Stewart Hart, Cass Hoskins, Clare Hunt, Paul A. James, Mark A. Jenkins, Alexa Kidd, Judy Kirk, Jessica Koehler, James Kollias, Sunil R. Lakhani, Mitchell G. Lawrence, Geoffrey J. Lindeman, Lara Lipton, Liz Lobb, Graham J. Mann, Sue Anne McLachlan, Bettina Meiser, Roger L. Milne, Sophie Nightingale, Shona O’Connell, Sarah O’Sullivan, David Gallego‐Ortega, Nick Pachter, Briony Patterson, Amy Pearn, Ellen Pieper, Edwina Rickard, Bridget A. Robinson, Mona Saleh, Elizabeth Salisbury, Christobel Saunders, Jodi M. Saunus, Clare L. Scott, Adrienne Sexton, Andrew N. Shelling, Melissa C. Southey, Amanda B. Spurdle, Jessica Taylor, Renea A. Taylor, Heather Thorne, Alison H. Trainer, Kathy Tucker, Jane E. Visvader, Logan C. Walker, Rachael Williams, Ingrid Winship, Mary Ann Young, Agnes Jager, Anna Jakubowska, Esther M. John, Audrey Jung, Rudolf Kaaks, Pooja Middha, Renske Keeman, Э. К. Хуснутдинова, Cari M. Kitahara, Linetta B. Koppert, Stella Koutros, Vessela N. Kristensen, Allison W. Kurian, James Lacey, Diether Lambrechts, Loı̈c Le Marchand, Wing‐Yee Lo, Jan Lubiński, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Marı́a Elena Martı́nez, Dimitrios Mavroudis, Usha Menon, Taru Muranen, Heli Nevanlinna, William G. Newman, Børge G. Nordestgaard, Kenneth Offit, Andrew F. Olshan, Håkan Olsson, Tjoung‐Won Park‐Simon, Paolo Peterlongo, Julian Peto, Dijana Plaseska‐Karanfilska, Nadège Presneau, Paolo Radice, Gad Rennert, Hedy S. Rennert, Atocha Romero, Emmanouil Saloustros, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Minouk J. Schoemaker, Lukas Schwentner, Christopher G. Scott, Mitul Shah, Xiao-Ou Shu, Jacques Simard, Ann Smeets, John J. Spinelli, Victoria L. Stevens, Anthony J. Swerdlow, Rulla M. Tamimi, William Tapper, Jack A. Taylor, Mary Beth Terry, Ian Tomlinson, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Elke M. van Veen, Joseph Vijai, Sophia Wang, Camilla Wendt, Robert Winqvist, Alicja Wolk, Argyrios Ziogas, Alison M. Dunning, Paul D.P. Pharoah, Douglas F. Easton, Wei Zheng, Peter Kraft, Jenny Chang‐Claude
Bibliographic record
VenueBritish Journal of Cancer · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversity of British ColumbiaUniversité LavalCentre hospitalier universitaire de QuébecMcGill UniversityUniversity of TorontoRoyal Victoria HospitalQueen's UniversityLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersDivision of Cancer Epidemiology and Genetics, National Cancer InstituteMedical Research and Materiel CommandServicio Gallego de SaludInstituto de Salud Carlos IIIMedical Research CouncilEuropean CommissionCanadian Institutes of Health ResearchDivision of Cancer Prevention, National Cancer InstituteNational Institutes of HealthHellenic Health FoundationFreistaat SachsenDeutschen Konsortium für Translationale KrebsforschungUniversitätsklinikum Hamburg-EppendorfXunta de GaliciaMutuelle Générale de l'Education NationaleInstitut Gustave-RoussyMinistero dello Sviluppo EconomicoNational Institute for Health and Care ResearchCenters for Disease Control and PreventionCancer Council South AustraliaMemorial Sloan-Kettering Cancer CenterCentre International de Recherche sur le CancerKreftforeningenInstitut National Du CancerDeutsche KrebshilfeNational Health and Medical Research CouncilUniversity of California, IrvineOulun YliopistoCancer Institute NSWMedizinischen Hochschule HannoverScottish GovernmentKWF KankerbestrijdingVetenskapsrådetNorges ForskningsrådStockholms Läns LandstingUniversity of WestminsterLigue Contre le CancerKuopion Yliopistollinen SairaalaUniversity of Southern CaliforniaCancerfondenCancer Council TasmaniaItä-Suomen YliopistoEberhard Karls Universität TübingenAmerican Cancer SocietyCancer AustraliaRussian Foundation for Basic ResearchUniversity of CreteInstitut National de la Santé et de la Recherche MédicaleProgramme Grants for Applied ResearchRobert Bosch StiftungAcademy of FinlandGentofte HospitalKing's College LondonWorld Cancer Research FundScottish Funding CouncilUniversity College LondonStavros Niarchos FoundationFondation de FranceNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchBreast Cancer CampaignNational Cancer InstituteEuropean Regional Development FundMinisterio de Sanidad, Servicios Sociales e IgualdadUniversity of CambridgeGovernment of CanadaFondation du cancer du sein du QuébecGénome QuébecNational Breast Cancer FoundationAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailNational Institute of Environmental Health SciencesSwedish Cancer FoundationAgency for Science, Technology and ResearchLon V. Smith FoundationMinistère du Développement Économique, de l’Innovation et de l’ExportationMcGill University Health CentreDavid F. and Margaret T. Grohne Family FoundationCentre Hospitalier Universitaire de QuébecGenome CanadaSundhed og Sygdom, Det Frie ForskningsrådDeutsches KrebsforschungszentrumDeutsche Gesetzliche UnfallversicherungDeutsche ForschungsgemeinschaftBreast Cancer Research FoundationMcGill UniversityAssociazione Italiana per la Ricerca sul CancroKarolinska InstitutetHarvard T.H. Chan School of Public HealthMinistry of Science and Higher Education of the Russian FederationU.S. ArmyUniversité LavalAgence Nationale de la RechercheWellcome TrustCancer Council VictoriaCalifornia Department of Public HealthBrigham and Women's HospitalRheinische Friedrich-Wilhelms-Universität BonnOak FoundationCancer Research UKBeckman Research Institute, City of HopeCancer Council NSWSusan G. Komen for the CureU.S. Department of Health and Human ServicesChief Scientist Office, Scottish Government Health and Social Care DirectorateMinisterio de Economía y CompetitividadBundesministerium für Bildung und ForschungOvarian Cancer Research FundFonds Wetenschappelijk Onderzoek
KeywordsBreast cancerMedicineOncologyMendelian randomizationCancerInternal medicineGeneticsBiologyGenotypeGeneGenetic variants
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.040
metaresearch head score (Gemma)0.094
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.040
Threshold uncertainty score0.214
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.040 | 0.094 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.010
GPT teacher head0.283
Teacher spread0.273 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations23
Published2021
Admission routes2
Has abstractyes