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Abstract
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.
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1 Section of Hygiene - Institute of Public Health, Università Cattolica del Sacro Cuore, L.go F. Vito, 1, Rome, Italy
2 International Agency for Research on Cancer (IARC), Lyon, France
3 Department of Hygiene, Epidemiology and Medical Statistics, University of Athens School of Medicine, Athens, Greece
4 Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
5 University of Turin, Department of Medical Sciences, Unit of Cancer Epidemiology, Turin, Italy
6 Cancer Registry of Norway, Oslo, Norway
7 Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L’Hospitalet de Llobregat, Catalonia, Spain
8 Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L’Hospitalet de Llobregat, Catalonia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
9 School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom
10 General Hospital of Pordenone, Pordenone, Italy
11 Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy; MRC-HPA Centre for Environment and Health, Respiratory Epidemiology and Public Health, National Heart and Lung Institute, Imperial College, London, United Kingdom
12 University of Manchester, School of Dentistry, Manchester, United Kingdom
13 University of Glasgow Dental School, Glasgow, Scotland, United Kingdom
14 Croatian National Cancer Registry, Croatian National Institute of Public Health, Zagreb, Croatia
15 Trinity College School of Dental Science, Dublin, Ireland
16 Leibniz Institute for Prevention Research and Epidemiology—BIPS, Bremen, Germany; Faculty of Mathematics and Computer Science, University of Bremen, Bremen, Germany
17 Institute of Carcinogenesis, Cancer Research Centre, Moscow, Russian Federation
18 Department of Epidemiology, Institute of Occupational Medicine, Lodz, Poland
19 Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
20 Regional Authority of Public Health, Banska Bystrica, Slovakia
21 Saint Mary General and Esophageal Surgery Clinic, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
22 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and Masaryk University, Brno, Czech Republic
23 Palacky University, Olomouc, Czech Republic
24 Section of Hygiene, Institute of Public Health, Università Cattolica del Sacro Cuore, IRCCS Fondazione Policlinico ‘Agostino Gemelli’, Rome, Italy