A Multivariable Mendelian Randomization Analysis Investigating Smoking and Alcohol Consumption in Oral and Oropharyngeal Cancer

Citation

Gormley, Mark; Dudding, Tom; Sanderson, Eleanor; Martin, Richard M.; Thomas, Steven; Tyrrell, Jessica; Ness, Andrew R.; Brennan, Paul; Munafò, Marcus; & Pring, Miranda, et al. (2020). A Multivariable Mendelian Randomization Analysis Investigating Smoking and Alcohol Consumption in Oral and Oropharyngeal Cancer. Nature Communications, 11(1), 6071. PMCID: PMC7695733

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.

URL

http://dx.doi.org/10.1038/s41467-020-19822-6

Reference Type

Journal Article

Year Published

2020

Journal Title

Nature Communications

Author(s)

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.

Article Type

Regular

PMCID

PMC7695733

Data Set/Study

GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN)
UK Biobank Study
GWAS of Oral and Oropharyngeal Cancer Conducted by the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network

Continent/Country

Nonspecific

ORCiD

Olshan - 0000-0001-9115-5128