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 - 2020/12/1
Y1 - 2020/12/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85096776478&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-19822-6
DO - 10.1038/s41467-020-19822-6
M3 - Article
C2 - 33247085
AN - SCOPUS:85096776478
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -
