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.

Details

Title
Genetic Contributions to The Association Between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis
Author
Pastorino, Roberta 1 ; Puggina, Anna 1 ; Carreras-Torres, Robert 2 ; Lagiou, Pagona 3 ; Holcátová, Ivana 4 ; Richiardi, Lorenzo 5 ; Kjaerheim, Kristina 6 ; Agudo, Antonio 7 ; Castellsagué, Xavier 8 ; Macfarlane, Tatiana V 9 ; Barzan, Luigi 10 ; Canova, Cristina 11 ; Thakker, Nalin S 12 ; Conway, David I 13 ; Znaor, Ariana 14 ; Healy, Claire M 15 ; Ahrens, Wolfgang 16 ; Zaridze, David 17 ; Szeszenia-Dabrowska, Neonilia 18 ; Lissowska, Jolanta 19 ; Fabianova, Eleonora 20 ; Ioan Nicolae Mates 21 ; Bencko, Vladimir 4 ; Foretova, Lenka 22 ; Janout, Vladimir 23 ; Brennan, Paul 2 ; Gaborieau, Valérie 2 ; McKay, James D 2 ; Boccia, Stefania 24 

 Section of Hygiene - Institute of Public Health, Università Cattolica del Sacro Cuore, L.go F. Vito, 1, Rome, Italy 
 International Agency for Research on Cancer (IARC), Lyon, France 
 Department of Hygiene, Epidemiology and Medical Statistics, University of Athens School of Medicine, Athens, Greece 
 Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic 
 University of Turin, Department of Medical Sciences, Unit of Cancer Epidemiology, Turin, Italy 
 Cancer Registry of Norway, Oslo, Norway 
 Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L’Hospitalet de Llobregat, Catalonia, Spain 
 Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L’Hospitalet de Llobregat, Catalonia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain 
 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 
Pages
1-6
Publication year
2018
Publication date
Mar 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2013960979
Copyright
© 2018. 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.