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

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, Paul Brennan, D. Neil Hayes, Eleanor Sanderson, M. Catherine Brown, Sophie Huang, Scott V. Bratman, Anna Spreafico, John Almeida, Joel C. Davies, Laura Bierut, Gary J. Macfarlane, Pagona Lagiou, Areti Lagiou, Jerry Polesel, Antonio Agudo, Laia Alemany, Wolfgang Ahrens, Claire M. Healy, David I. Conway, Mari Nygard, Cristina Canova, Ivana Holcatova, Lorenzo Richiardi, Ariana Znaor, David P. Goldstein, Rayjean J. Hung, Wei Xu, Geoffrey Liu () and Osvaldo Espin-Garcia
Additional contact information
Abhinav Thakral: University of Toronto
John JW. Lee: University of Toronto
Tianzhichao Hou: University of Toronto
Katrina Hueniken: University of Toronto
Tom Dudding: University of Bristol
Mark Gormley: University of Bristol
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
Scott V. Bratman: University Health Network
Anna Spreafico: University Health Network
John Almeida: University of Toronto
Joel C. Davies: University of Toronto
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
Rayjean J. Hung: Sinai Health
Wei Xu: University of Toronto
Geoffrey Liu: German Cancer Research Center (DKFZ)
Osvaldo Espin-Garcia: University of Toronto

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-51679-x

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