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.

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.

Details

Title
A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer
Author
Gormley, Mark 1   VIAFID ORCID Logo  ; Dudding, Tom 1   VIAFID ORCID Logo  ; Sanderson, Eleanor 2   VIAFID ORCID Logo  ; Martin, Richard M 3   VIAFID ORCID Logo  ; Thomas, Steven 4 ; Tyrrell, Jessica 5   VIAFID ORCID Logo  ; Ness, Andrew R 6 ; Brennan, Paul 7   VIAFID ORCID Logo  ; Munafò Marcus 8   VIAFID ORCID Logo  ; Pring Miranda 9 ; Boccia Stefania 10 ; Olshan, Andrew F 11 ; Diergaarde Brenda 12 ; Hung, Rayjean J 13   VIAFID ORCID Logo  ; Liu, Geoffrey 14 ; Davey Smith George 2   VIAFID ORCID Logo  ; Richmond, Rebecca C 2   VIAFID ORCID Logo 

1  University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Bristol Dental Hospital and School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Department of Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
2  University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Department of Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
3  University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Department of Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University Hospitals Bristol and Weston NHS Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
4  University of Bristol, Bristol Dental Hospital and School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University Hospitals Bristol and Weston NHS Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
5  University of Exeter Medical School, RD&E Hospital, Exeter, UK (GRID:grid.8391.3) (ISNI:0000 0004 1936 8024) 
6  University Hospitals Bristol and Weston NHS Foundation Trust National Institute for Health Research Bristol Biomedical Research Centre, University of Bristol, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
7  Genetic Epidemiology Group, World Health Organization, International Agency for Research on Cancer, Lyon, France (GRID:grid.17703.32) (ISNI:0000000405980095) 
8  University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, Department of Population Health Sciences, Bristol Medical School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); University of Bristol, School of Psychological Science, Faculty of Life Sciences, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
9  University of Bristol, Bristol Dental Hospital and School, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
10  Università Cattolica del Sacro Cuore, Section of Hygiene, University Department of Life Sciences and Public Health, Roma, Italia (GRID:grid.8142.f) (ISNI:0000 0001 0941 3192); Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Woman and Child Health and Public Health-Public Health Area, Roma, Italy (GRID:grid.414603.4) 
11  University of North Carolina, Department of Epidemiology, Gillings School of Global Public Health, Chapel Hill, USA (GRID:grid.410711.2) (ISNI:0000 0001 1034 1720) 
12  University of Pittsburgh, and UPMC Hillman Cancer Center, Department of Human Genetics, Graduate School of Public Health, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
13  Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada (GRID:grid.250674.2) (ISNI:0000 0004 0626 6184); University of Toronto, Dalla Lana School of Public Health, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938) 
14  University of Toronto, Dalla Lana School of Public Health, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); Princess Margaret Cancer Centre, Toronto, Canada (GRID:grid.415224.4) (ISNI:0000 0001 2150 066X) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-19822-6
ProQuest document ID
2473274168
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.