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

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...

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Published in:Nature communications Vol. 15; no. 1; pp. 7835 - 9
Main Authors: Thakral, Abhinav, Lee, John JW, Hou, Tianzhichao, Hueniken, Katrina, Dudding, Tom, Gormley, Mark, Virani, Shama, Olshan, Andrew, Diergaarde, Brenda, Ness, Andrew R., Waterboer, Tim, Smith-Byrne, Karl, Brennan, Paul, Hayes, D. Neil, Sanderson, Eleanor, Brown, M. Catherine, Huang, Sophie, Bratman, Scott V., Spreafico, Anna, De Almeida, John, Davies, Joel C., Bierut, Laura, Macfarlane, Gary J., Lagiou, Pagona, Lagiou, Areti, Polesel, Jerry, Agudo, Antonio, Alemany, Laia, Ahrens, Wolfgang, Healy, Claire M., Conway, David I., Nygard, Mari, Canova, Cristina, Holcatova, Ivana, Richiardi, Lorenzo, Znaor, Ariana, Goldstein, David P., Hung, Rayjean J., Xu, Wei, Liu, Geoffrey, Espin-Garcia, Osvaldo
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 07.09.2024
Nature Publishing Group
Nature Portfolio
Subjects:
45/43
631/67/1536
631/67/2324
Alcohol
Alcohol Drinking - adverse effects
Alcohols
Cancer
Case-Control Studies
Female
Head & neck cancer
Head and neck carcinoma
Head and Neck Neoplasms - epidemiology
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - virology
Human papillomavirus
Humanities and Social Sciences
Humans
Male
Mendelian Randomization Analysis
Middle Aged
multidisciplinary
Multivariable control
Papillomaviridae - genetics
Papillomavirus Infections - epidemiology
Papillomavirus Infections - virology
Polymorphism, Single Nucleotide
Randomization
Risk Factors
Science
Science (multidisciplinary)
Smoking
Smoking - adverse effects
Squamous cell carcinoma
Squamous Cell Carcinoma of Head and Neck - epidemiology
Squamous Cell Carcinoma of Head and Neck - genetics
Squamous Cell Carcinoma of Head and Neck - virology
ISSN:2041-1723, 2041-1723
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Summary: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. Head and neck squamous cell carcinoma can occur with and without the presence of HPV infection. Here, the authors utilise Mendelian randomization to assess the causal effects of smoking and alcohol on HPV-positive and HPV-negative head and neck cancer development.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-51679-x