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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Hanla A Park
  • Sonja Neumeyer
  • Kyriaki Michailidou
  • Manjeet K Bolla
  • Qin Wang
  • Joe Dennis
  • Thomas U Ahearn
  • Irene L Andrulis
  • Hoda Anton-Culver
  • Natalia N Antonenkova
  • Volker Arndt
  • Kristan J Aronson
  • Annelie Augustinsson
  • 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
  • Sara Y Brucker
  • Barbara Burwinkel
  • Daniele Campa
  • Federico Canzian
  • Jose E Castelao
  • Stephen J Chanock
  • Georgia Chenevix-Trench
  • Christine L Clarke
  • Don M 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
  • Børge G Nordestgaard
  • NBCS Collaborators
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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.

Original languageEnglish
JournalBritish Journal of Cancer
Issue number8
Pages (from-to)1135-1145
Number of pages11
Publication statusPublished - 12 Oct 2021

ID: 66966156