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

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 Mendeli...

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Published in:Nature communications Vol. 11; no. 1; pp. 6071 - 10
Main Authors: Gormley, Mark, Dudding, Tom, Sanderson, Eleanor, Martin, Richard M., Thomas, Steven, Tyrrell, Jessica, Ness, Andrew R., Brennan, Paul, Munafò, Marcus, Pring, Miranda, Boccia, Stefania, Olshan, Andrew F., Diergaarde, Brenda, Hung, Rayjean J., Liu, Geoffrey, Davey Smith, George, Richmond, Rebecca C.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 27.11.2020
Nature Publishing Group
Nature Portfolio
Subjects:
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45/43
631/114
631/67/1536
631/67/1665
631/67/2195
Alcohol
Alcohol Drinking - genetics
Alcohol use
Alcoholic beverages
Alcohols
Cancer
Genetic Predisposition to Disease
Genome-wide association studies
Genome-Wide Association Study
Genomes
Head & neck cancer
Health risks
Humanities and Social Sciences
Humans
Mendelian Randomization Analysis
Mouth Neoplasms - genetics
multidisciplinary
Multivariate Analysis
Observational studies
Oral cancer
Oropharyngeal cancer
Oropharyngeal Neoplasms - genetics
Polymorphism, Single Nucleotide - genetics
Randomization
Risk analysis
Risk Factors
Science
Science (multidisciplinary)
Sexual Partners
Smoking
Smoking - genetics
Standard deviation
Synergistic effect
Throat cancer
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Alcohol and smoking are both associated with oral/oropharyngeal cancer risk, but independent effects are unclear given their relatedness. Here, the authors use multivariable Mendelian randomization to show that both alcohol and smoking are independently causal for oral/oropharyngeal cancer.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-19822-6