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A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer

Author

Listed:
  • Mark Gormley

    (University of Bristol
    University of Bristol
    University of Bristol)

  • Tom Dudding

    (University of Bristol
    University of Bristol
    University of Bristol)

  • Eleanor Sanderson

    (University of Bristol
    University of Bristol)

  • Richard M. Martin

    (University of Bristol
    University of Bristol
    University Hospitals Bristol and Weston NHS Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol)

  • Steven Thomas

    (University of Bristol
    University Hospitals Bristol and Weston NHS Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol)

  • Jessica Tyrrell

    (University of Exeter Medical School)

  • Andrew R. Ness

    (University Hospitals Bristol and Weston NHS Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol)

  • Paul Brennan

    (Genetic Epidemiology Group, World Health Organization, International Agency for Research on Cancer)

  • Marcus Munafò

    (University of Bristol
    University of Bristol
    University of Bristol)

  • Miranda Pring

    (University of Bristol)

  • Stefania Boccia

    (Università Cattolica del Sacro Cuore
    Fondazione Policlinico Universitario A. Gemelli IRCCS)

  • Andrew F. Olshan

    (University of North Carolina)

  • Brenda Diergaarde

    (University of Pittsburgh, and UPMC Hillman Cancer Center)

  • Rayjean J. Hung

    (Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System
    University of Toronto)

  • Geoffrey Liu

    (University of Toronto
    Princess Margaret Cancer Centre)

  • George Davey Smith

    (University of Bristol
    University of Bristol)

  • Rebecca C. Richmond

    (University of Bristol
    University of Bristol)

Abstract

The independent effects of smoking and alcohol in head and neck cancer are not clear, given the strong association between these risk factors. Their apparent synergistic effect reported in previous observational studies may also underestimate independent effects. Here we report multivariable Mendelian randomization performed in a two-sample approach using summary data on 6,034 oral/oropharyngeal cases and 6,585 controls from a recent genome-wide association study. Our results demonstrate strong evidence for an independent causal effect of smoking on oral/oropharyngeal cancer (IVW OR 2.6, 95% CI = 1.7, 3.9 per standard deviation increase in lifetime smoking behaviour) and an independent causal effect of alcohol consumption when controlling for smoking (IVW OR 2.1, 95% CI = 1.1, 3.8 per standard deviation increase in drinks consumed per week). This suggests the possibility that the causal effect of alcohol may have been underestimated. However, the extent to which alcohol is modified by smoking requires further investigation.

Suggested Citation

  • Mark Gormley & Tom Dudding & Eleanor Sanderson & Richard M. Martin & Steven Thomas & Jessica Tyrrell & Andrew R. Ness & Paul Brennan & Marcus Munafò & Miranda Pring & Stefania Boccia & Andrew F. Olsha, 2020. "A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19822-6
    DOI: 10.1038/s41467-020-19822-6
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    Cited by:

    1. Ruoyu Wang & Qihua Wang & Wang Miao, 2023. "A robust fusion-extraction procedure with summary statistics in the presence of biased sources," Biometrika, Biometrika Trust, vol. 110(4), pages 1023-1040.
    2. Abhinav Thakral & John JW. Lee & Tianzhichao Hou & Katrina Hueniken & Tom Dudding & Mark Gormley & Shama Virani & Andrew Olshan & Brenda Diergaarde & Andrew R. Ness & Tim Waterboer & Karl Smith-Byrne , 2024. "Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study," Nature Communications, Nature, vol. 15(1), pages 1-9, December.

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