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

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 Olshan; Brenda Diergaarde; Rayjean J. Hung; Geoffrey Liu; George Davey Smith; Rebecca C Richmond

doi:10.1038/s41467-020-19822-6

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

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 Olshan, Brenda Diergaarde, Rayjean J. Hung, Geoffrey Liu, George Davey Smith, Rebecca C Richmond

^*Corresponding author for this work

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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.

Original language	English
Article number	6071 (2020)
Number of pages	10
Journal	Nature Communications
Volume	11
DOIs	https://doi.org/10.1038/s41467-020-19822-6
Publication status	Published - 27 Nov 2020

Research Groups and Themes

Physical and Mental Health
Tobacco and Alcohol
ICEP

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Dr Mark Gormley
- mark.gormleybristol.acuk
- Bristol Dental School - Consultant Senior Lecturer
- Bristol Population Health Science Institute
- Cancer
Person: Academic , Member
Dr Miranda Pring
- Miranda.Pringbristol.acuk
- Bristol Dental School - Consultant Senior Lecturer in Oral Maxillofacial Pathology
Person: Academic

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Gormley, M., Dudding, T., Sanderson, E., Martin, R. M., Thomas, S., Tyrrell, J., Ness, A. R., Brennan, P., Munafò, M., Pring, M., Boccia, S., Olshan, A. F., Diergaarde, B., Hung, R. J., Liu, G., Davey Smith, G., & Richmond, R. C. (2020). A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer. Nature Communications, 11, Article 6071 (2020). https://doi.org/10.1038/s41467-020-19822-6

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title = "A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer",

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.",

author = "Mark Gormley and Tom Dudding and Eleanor Sanderson and Martin, {Richard M} and Steven Thomas and Jessica Tyrrell and Ness, {Andrew R} and Paul Brennan and Marcus Munaf{\`o} and Miranda Pring and Stefania Boccia and Olshan, {Andrew F} and Brenda Diergaarde and Hung, {Rayjean J.} and Geoffrey Liu and {Davey Smith}, George and Richmond, {Rebecca C}",

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Gormley, M , Dudding, T , Sanderson, E , Martin, RM , Thomas, S, Tyrrell, J, Ness, AR, Brennan, P, Munafò, M , Pring, M, Boccia, S, Olshan, AF, Diergaarde, B, Hung, RJ, Liu, G, Davey Smith, G & Richmond, RC 2020, 'A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer', Nature Communications, vol. 11, 6071 (2020). https://doi.org/10.1038/s41467-020-19822-6

TY - JOUR

T1 - A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer

AU - Gormley, Mark

AU - Dudding, Tom

AU - Sanderson, Eleanor

AU - Martin, Richard M

AU - Thomas, Steven

AU - Tyrrell, Jessica

AU - Ness, Andrew R

AU - Brennan, Paul

AU - Munafò, Marcus

AU - Pring, Miranda

AU - Boccia, Stefania

AU - Olshan, Andrew F

AU - Diergaarde, Brenda

AU - Hung, Rayjean J.

AU - Liu, Geoffrey

AU - Davey Smith, George

AU - Richmond, Rebecca C

PY - 2020/11/27

Y1 - 2020/11/27

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-19822-6

DO - 10.1038/s41467-020-19822-6

M3 - Article (Academic Journal)

C2 - 33247085

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

M1 - 6071 (2020)

ER -

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

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Dr Mark Gormley

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