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Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study

Author

Listed:
  • Abhinav Thakral

    (University of Toronto)

  • John JW. Lee

    (University of Toronto
    Sinai Health System)

  • Tianzhichao Hou

    (University of Toronto)

  • Katrina Hueniken

    (University of Toronto)

  • Tom Dudding

    (University of Bristol
    Avon Street)

  • Mark Gormley

    (University of Bristol
    Avon Street)

  • Shama Virani

    (World Health Organization)

  • Andrew Olshan

    (University of North Carolina)

  • Brenda Diergaarde

    (and UPMC Hillman Cancer Center)

  • Andrew R. Ness

    (University of Bristol)

  • Tim Waterboer

    (German Cancer Research Center (DKFZ))

  • Karl Smith-Byrne

    (World Health Organization)

  • Paul Brennan

    (World Health Organization)

  • D. Neil Hayes

    (University of Tennessee Health Science Center)

  • Eleanor Sanderson

    (University of Bristol)

  • M. Catherine Brown

    (University Health Network)

  • Sophie Huang

    (University Health Network
    University of Toronto)

  • Scott V. Bratman

    (University Health Network
    University of Toronto)

  • Anna Spreafico

    (University Health Network
    University of Toronto)

  • John Almeida

    (University of Toronto
    University Health Network)

  • Joel C. Davies

    (University of Toronto
    Sinai Health System)

  • Laura Bierut

    (Washington University School of Medicine)

  • Gary J. Macfarlane

    (University of Aberdeen)

  • Pagona Lagiou

    (University of Athens)

  • Areti Lagiou

    (University of West Attica)

  • Jerry Polesel

    (Centro di Riferimento Oncologico di Aviano (CRO) IRCCS)

  • Antonio Agudo

    (Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)

  • Laia Alemany

    (Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)

  • Wolfgang Ahrens

    (University of Bremen)

  • Claire M. Healy

    (Trinity College Dublin)

  • David I. Conway

    (University of Glasgow)

  • Mari Nygard

    (Norwegian Institute of Public Health)

  • Cristina Canova

    (University of Padua)

  • Ivana Holcatova

    (Charles University)

  • Lorenzo Richiardi

    (University of Turin and CPO-Piemonte)

  • Ariana Znaor

    (World Health Organization)

  • David P. Goldstein

    (University of Toronto
    University Health Network)

  • Rayjean J. Hung

    (Sinai Health
    University of Toronto)

  • Wei Xu

    (University of Toronto
    University of Toronto)

  • Geoffrey Liu

    (German Cancer Research Center (DKFZ)
    University Health Network
    University of Toronto)

  • Osvaldo Espin-Garcia

    (University of Toronto
    University of Toronto
    University of Western Ontario)

Abstract

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51679-x
    DOI: 10.1038/s41467-024-51679-x
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    References listed on IDEAS

    as
    1. Nick Patterson & Alkes L Price & David Reich, 2006. "Population Structure and Eigenanalysis," PLOS Genetics, Public Library of Science, vol. 2(12), pages 1-20, December.
    2. 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.
    3. Aida Ferreiro-Iglesias & James D. McKay & Nicole Brenner & Shama Virani & Corina Lesseur & Valerie Gaborieau & Andy R. Ness & Rayjean J. Hung & Geoffrey Liu & Brenda Diergaarde & Andrew F. Olshan & Ne, 2021. "Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
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