With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.

Cancer Epidemiology Research Program Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Catalonia Spain

Cancer Registry of Norway Oslo Norway

CIBER Epidemiología y Salud Pública Barcelona Spain

Croatian National Cancer Registry Croatian National Institute of Public Health Zagreb Croatia

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute and Masaryk University Brno Czech Republic

Department of Cancer Epidemiology and Prevention M Sklodowska Curie Memorial Cancer Center and Institute of Oncology Warsaw Poland

Department of Environmental Medicine and Public Health University of Padova Padova Italy

Department of Epidemiology Institute of Occupational Medicine Lodz Poland

Department of Hygiene Epidemiology and Medical Statistics University of Athens School of Medicine Athens Greece

Faculty of Mathematics and Computer Science University of Bremen Bremen Germany

General Hospital of Pordenone Pordenone Italy

Institute of Carcinogenesis Cancer Research Centre Moscow Russian Federation

Institute of Hygiene and Epidemiology 1st Faculty of Medicine Charles University Prague Czech Republic

International Agency for Research on Cancer Lyon France

Leibniz Institute for Prevention Research and Epidemiology BIPS Bremen Germany

MRC HPA Centre for Environment and Health Respiratory Epidemiology and Public Health National Heart and Lung Institute Imperial College London United Kingdom

Palacky University Olomouc Czech Republic

Regional Authority of Public Health Banska Bystrica Slovakia

Saint Mary General and Esophageal Surgery Clinic Carol Davila University of Medicine and Pharmacy Bucharest Romania

School of Medicine and Dentistry University of Aberdeen Aberdeen United Kingdom

Section of Hygiene Institute of Public Health Università Cattolica del Sacro Cuore IRCCS Fondazione Policlinico 'Agostino Gemelli' Rome Italy

Section of Hygiene Institute of Public Health Università Cattolica del Sacro Cuore L go F Vito 1 00168 Rome Italy

Trinity College School of Dental Science Dublin Ireland

University of Glasgow Dental School Glasgow Scotland United Kingdom

University of Manchester School of Dentistry Manchester United Kingdom

University of Turin Department of Medical Sciences Unit of Cancer Epidemiology Turin Italy

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