SCIenTIFIC REPoRTS | (2018) 8:4534 | DOI:10.1038/s41598-018-22626-w
Genetic Contributions to The
Association Between Adult Height
and Head and Neck Cancer: A
Mendelian Randomization Analysis
, Anna Puggina
, Robert Carreras-Torres
, Pagona Lagiou
, Lorenzo Richiardi
, Kristina Kjaerheim
, Antonio Agudo
, Xavier Castellsagué
Tatiana V. Macfarlane
, Luigi Barzan
, Cristina Canova
, Nalin S. Thakker
, David I.
, Ariana Znaor
, Claire M. Healy
, Wolfgang Ahrens
, David Zaridze
, Jolanta Lissowska
, Eleonora Fabianova
, Ioan Nicolae Mates
, Lenka Foretova
, Vladimir Janout
, Paul Brennan
, Valérie Gaborieau
James D. McKay
& Stefania Boccia
With the aim to dissect the eect 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 identied 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% Condence Interval
(95%CI), 0.99–1.32). The association analyses with potential confounders revealed that the GRS was
Section of Hygiene - Institute of Public Health, Università Cattolica del Sacro Cuore, L.go F. Vito, 1, 00168, Rome,
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.
Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L’Hospitalet de Llobregat,
CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
School of Medicine and
Dentistry, University of Aberdeen, Aberdeen, United Kingdom.
General Hospital of Pordenone, Pordenone, Italy.
Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy.
for Environment and Health, Respiratory Epidemiology and Public Health, National Heart and Lung Institute,
Imperial College, London, United Kingdom.
University of Manchester, School of Dentistry, Manchester, United
University of Glasgow Dental School, Glasgow, Scotland, United Kingdom.
Croatian National Cancer
Registry, Croatian National Institute of Public Health, Zagreb, Croatia.
Trinity College School of Dental Science,
Leibniz Institute for Prevention Research and Epidemiology—BIPS, Bremen, Germany.
Mathematics and Computer Science, University of Bremen, Bremen, Germany.
Institute of Carcinogenesis, Cancer
Research Centre, Moscow, Russian Federation.
Department of Epidemiology, Institute of Occupational Medicine,
Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer
Center and Institute of Oncology, Warsaw, Poland.
Regional Authority of Public Health, Banska Bystrica, Slovakia.
Saint Mary General and Esophageal Surgery Clinic, Carol Davila University of Medicine and Pharmacy, Bucharest,
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and Masaryk
University, Brno, Czech Republic.
Palacky University, Olomouc, Czech Republic.
Section of Hygiene, Institute of
Public Health, Università Cattolica del Sacro Cuore, IRCCS Fondazione Policlinico ‘Agostino Gemelli’, Rome, Italy.
Roberta Pastorino, Anna Puggina and Robert Carreras-Torres contributed equally to this work. Correspondence and
requests for materials should be addressed to A.P. (email: firstname.lastname@example.org)
Received: 3 May 2017
Accepted: 19 February 2018
Published: xx xx xxxx