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.
N1 - Funding Information:
M.G. was a National Institute for Health Research (NIHR) academic clinical fellow and is currently supported by a Wellcome Trust GW4-Clinical Academic Training PhD Fellowship. This research was funded in part, by the Wellcome Trust [Grant number 220530/Z/20/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. M.G. also received a bursary from the Association of British Academic Oral and Maxillofacial Surgeons (ABAOMS) to help support this work. R.C.R. is a de Pass VC research fellow at the University of Bristol. J.T. is supported by an Academy of Medical Sciences (AMS) Springboard award, which is supported by the AMS, the Wellcome Trust, Global Challenges Research Fund (GCRF), the Government Department of Business, Energy and Industrial strategy, the British Heart Foundation and Diabetes UK (SBF004\1079). R.M.M. was supported by a Cancer Research UK (C18281/A19169) programme grant (the Integrative Cancer Epidemiology Programme) and is part of the Medical Research Council Integrative Epidemiology Unit at the University of Bristol supported by the Medical Research Council (MC_UU_12013/1, MC_UU_12013/2, and MC_UU_12013/3) and the University of Bristol. R.M.M. and A.R.N. are supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre which is funded by the National Institute for Health Research (NIHR) and is a partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. This publication presents data from the Head and Neck 5000 study. The study was a component of independent research funded by the NIHR under its Programme Grants for Applied Research scheme (RP-PG-0707-10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Core funding was also provided through awards from Above and Beyond, University Hospitals Bristol Research Capability Funding and the NIHR Senior Investigator award to A.R.N. B.D. and the University of Pittsburgh head and neck cancer case-control study are supported by US National Institutes of Health (NIH) grants: P50 CA097190, P30 CA047904 and R01 DE025712. The genotyping of the HNSCC cases and controls was performed at the Center for Inherited Disease Research (CIDR) and funded by the US National Institute of Dental and Craniofacial Research (NIDCR; 1X01HG007780-0). The University of North Carolina (UNC) CHANCE study was supported in part by the National Cancer Institute (R01-CA90731).
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
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.
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U2 - 10.1038/s41467-020-19822-6
DO - 10.1038/s41467-020-19822-6
M3 - Article
C2 - 33247085
AN - SCOPUS:85096776478
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 6071
ER -