TY - JOUR
T1 - Genetic Contributions to the Association between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis
AU - Pastorino, Roberta
AU - Puggina, Anna
AU - Carreras-Torres, Robert
AU - Lagiou, Pagona
AU - Holcátová, Ivana
AU - Richiardi, Lorenzo
AU - Kjaerheim, Kristina
AU - Agudo, Antonio
AU - Castellsagué, Xavier
AU - Macfarlane, Tatiana V.
AU - Barzan, Luigi
AU - Canova, Cristina
AU - Thakker, Nalin S.
AU - Conway, David I.
AU - Znaor, Ariana
AU - Healy, Claire M.
AU - Ahrens, Wolfgang
AU - Zaridze, David
AU - Szeszenia-Dabrowska, Neonilia
AU - Lissowska, Jolanta
AU - Fabianova, Eleonora
AU - Mates, Ioan Nicolae
AU - Bencko, Vladimir
AU - Foretova, Lenka
AU - Janout, Vladimir
AU - Brennan, Paul
AU - Gaborieau, Valérie
AU - Mckay, James D.
AU - Boccia, Stefania
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - EPIDEMIOLOGY CONSORTIUM
KW - POOLED ANALYSIS
KW - PROSPECTIVE COHORT
KW - RISK-FACTORS
KW - EPIDEMIOLOGY CONSORTIUM
KW - POOLED ANALYSIS
KW - PROSPECTIVE COHORT
KW - RISK-FACTORS
UR - http://hdl.handle.net/10807/122176
UR - http://www.nature.com/srep/index.html
U2 - 10.1038/s41598-018-22626-w
DO - 10.1038/s41598-018-22626-w
M3 - Article
SN - 2045-2322
VL - 8
SP - N/A-N/A
JO - Scientific Reports
JF - Scientific Reports
ER -