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 De 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; Osvaldo Espin-Garcia

doi:10.1038/s41467-024-51679-x

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 De AlmeidaJoel 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, Osvaldo Espin-Garcia

^*Corresponding author for this work

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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.

Original language	English
Article number	7835
Journal	Nature Communications
Volume	15
DOIs	https://doi.org/10.1038/s41467-024-51679-x
Publication status	Published - 7 Sept 2024

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© The Author(s) 2024.

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Thakral, A., Lee, J. JW., Hou, T., Hueniken, K., Dudding, T., Gormley, M., Virani, S., Olshan, A., Diergaarde, B., Ness, A. R., Waterboer, T., Smith-Byrne, K., Brennan, P., Hayes, D. N., Sanderson, E., Brown, M. C., Huang, S., Bratman, S. V., Spreafico, A., ... Espin-Garcia, O. (2024). Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study. Nature Communications, 15, Article 7835. https://doi.org/10.1038/s41467-024-51679-x

@article{3ada1cef96da4b8bbb744429f03b9589,

title = "Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study",

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.",

author = "Abhinav Thakral and Lee, {John JW.} and Tianzhichao Hou and Katrina Hueniken and Tom Dudding and Mark Gormley and Shama Virani and Andrew Olshan and Brenda Diergaarde and Ness, {Andrew R.} and Tim Waterboer and Karl Smith-Byrne and Paul Brennan and Hayes, {D. Neil} and Eleanor Sanderson and Brown, {M. Catherine} and Sophie Huang and Bratman, {Scott V.} and Anna Spreafico and Almeida, {John De} and Davies, {Joel C.} and Laura Bierut and Macfarlane, {Gary J.} and Pagona Lagiou and Areti Lagiou and Jerry Polesel and Antonio Agudo and Laia Alemany and Wolfgang Ahrens and Healy, {Claire M.} and Conway, {David I.} and Mari Nygard and Cristina Canova and Ivana Holcatova and Lorenzo Richiardi and Ariana Znaor and Goldstein, {David P.} and Hung, {Rayjean J.} and Wei Xu and Geoffrey Liu and Osvaldo Espin-Garcia",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = sep,

day = "7",

doi = "10.1038/s41467-024-51679-x",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Springer Nature",

}

Thakral, A, Lee, JJW, Hou, T, Hueniken, K, Dudding, T , Gormley, M, Virani, S, Olshan, A, Diergaarde, B, Ness, AR, Waterboer, T, Smith-Byrne, K, Brennan, P, Hayes, DN, Sanderson, E, Brown, MC, Huang, S, Bratman, SV, Spreafico, A, Almeida, JD, Davies, JC, Bierut, L, Macfarlane, GJ, Lagiou, P, Lagiou, A, Polesel, J, Agudo, A, Alemany, L, Ahrens, W, Healy, CM, Conway, DI, Nygard, M, Canova, C, Holcatova, I, Richiardi, L, Znaor, A, Goldstein, DP, Hung, RJ, Xu, W, Liu, G & Espin-Garcia, O 2024, 'Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study', Nature Communications, vol. 15, 7835. https://doi.org/10.1038/s41467-024-51679-x

TY - JOUR

T1 - Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study

AU - Thakral, Abhinav

AU - Lee, John JW.

AU - Hou, Tianzhichao

AU - Hueniken, Katrina

AU - Dudding, Tom

AU - Gormley, Mark

AU - Virani, Shama

AU - Olshan, Andrew

AU - Diergaarde, Brenda

AU - Ness, Andrew R.

AU - Waterboer, Tim

AU - Smith-Byrne, Karl

AU - Brennan, Paul

AU - Hayes, D. Neil

AU - Sanderson, Eleanor

AU - Brown, M. Catherine

AU - Huang, Sophie

AU - Bratman, Scott V.

AU - Spreafico, Anna

AU - Almeida, John De

AU - Davies, Joel C.

AU - Bierut, Laura

AU - Macfarlane, Gary J.

AU - Lagiou, Pagona

AU - Lagiou, Areti

AU - Polesel, Jerry

AU - Agudo, Antonio

AU - Alemany, Laia

AU - Ahrens, Wolfgang

AU - Healy, Claire M.

AU - Conway, David I.

AU - Nygard, Mari

AU - Canova, Cristina

AU - Holcatova, Ivana

AU - Richiardi, Lorenzo

AU - Znaor, Ariana

AU - Goldstein, David P.

AU - Hung, Rayjean J.

AU - Xu, Wei

AU - Liu, Geoffrey

AU - Espin-Garcia, Osvaldo

PY - 2024/9/7

Y1 - 2024/9/7

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-024-51679-x

DO - 10.1038/s41467-024-51679-x

M3 - Article (Academic Journal)

C2 - 39244563

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

M1 - 7835

ER -

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

Abstract

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