Genetic Contributions to the Association between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis

Roberta Pastorino; Anna Puggina; Robert Carreras-Torres; Pagona Lagiou; Ivana Holcátová; Lorenzo Richiardi; Kristina Kjaerheim; Antonio Agudo; Xavier Castellsagué; Tatiana V. Macfarlane; Luigi Barzan; Cristina Canova; Nalin S. Thakker; David I. Conway; Ariana Znaor; Claire M. Healy; Wolfgang Ahrens; David Zaridze; Neonilia Szeszenia-Dabrowska; Jolanta Lissowska; Eleonora Fabianova; Ioan Nicolae Mates; Vladimir Bencko; Lenka Foretova; Vladimir Janout; Paul Brennan; Valérie Gaborieau; James D. McKay; Stefania Boccia

doi:10.1038/s41598-018-22626-w

Genetic Contributions to the Association between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis

Roberta Pastorino, Anna Puggina^*, Robert Carreras-Torres, Pagona Lagiou, Ivana Holcátová, Lorenzo Richiardi, Kristina Kjaerheim, Antonio Agudo, Xavier Castellsagué, Tatiana V. Macfarlane, Luigi Barzan, Cristina Canova, Nalin S. Thakker, David I. Conway, Ariana Znaor, Claire M. Healy, Wolfgang Ahrens, David Zaridze, Neonilia Szeszenia-Dabrowska, Jolanta LissowskaEleonora Fabianova, Ioan Nicolae Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Paul Brennan, Valérie Gaborieau, James D. McKay, Stefania Boccia

^*Corresponding author for this work

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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.

Original language	English
Article number	4534
Journal	Scientific Reports
Volume	8
Early online date	14 Mar 2018
DOIs	https://doi.org/10.1038/s41598-018-22626-w
Publication status	Published - 1 Dec 2018

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Genetic Contributions to The Association Between Adult Height and Head and Neck Cancer
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Pastorino, R., Puggina, A., Carreras-Torres, R., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T. V., Barzan, L., Canova, C., Thakker, N. S., Conway, D. I., Znaor, A., Healy, C. M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., ... Boccia, S. (2018). Genetic Contributions to the Association between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis. Scientific Reports, 8, [4534]. https://doi.org/10.1038/s41598-018-22626-w

Pastorino, R, Puggina, A, Carreras-Torres, R, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, TV, Barzan, L, Canova, C, Thakker, NS, Conway, DI, Znaor, A, Healy, CM, Ahrens, W, Zaridze, D, Szeszenia-Dabrowska, N, Lissowska, J, Fabianova, E, Mates, IN, Bencko, V, Foretova, L, Janout, V, Brennan, P, Gaborieau, V, McKay, JD & Boccia, S 2018, 'Genetic Contributions to the Association between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis', Scientific Reports, vol. 8, 4534. https://doi.org/10.1038/s41598-018-22626-w

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title = "Genetic Contributions to the Association between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis",

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.",

author = "Roberta Pastorino and Anna Puggina and Robert Carreras-Torres and Pagona Lagiou and Ivana Holc{\'a}tov{\'a} and Lorenzo Richiardi and Kristina Kjaerheim and Antonio Agudo and Xavier Castellsagu{\'e} and Macfarlane, {Tatiana V.} and Luigi Barzan and Cristina Canova and Thakker, {Nalin S.} and Conway, {David I.} and Ariana Znaor and Healy, {Claire M.} and Wolfgang Ahrens and David Zaridze and Neonilia Szeszenia-Dabrowska and Jolanta Lissowska and Eleonora Fabianova and Mates, {Ioan Nicolae} and Vladimir Bencko and Lenka Foretova and Vladimir Janout and Paul Brennan and Val{\'e}rie Gaborieau and McKay, {James D.} and Stefania Boccia",

note = "Acknowledgements: The authors thank the Italian Association for Research on Cancer (AIRC, IG 2013 n. 14211) and the PRECeDI project (Marie Sk{\l}odowska-Curie Research and Innovation Staff Exchange - RISE N°645740) for supporting the work of Roberta Pastorino and Anna Puggina.",

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doi = "10.1038/s41598-018-22626-w",

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T1 - Genetic Contributions to the Association between Adult Height and Head and Neck Cancer

T2 - 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

N1 - Acknowledgements: The authors thank the Italian Association for Research on Cancer (AIRC, IG 2013 n. 14211) and the PRECeDI project (Marie Skłodowska-Curie Research and Innovation Staff Exchange - RISE N°645740) for supporting the work of Roberta Pastorino and Anna Puggina.

PY - 2018/12/1

Y1 - 2018/12/1

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.

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U2 - 10.1038/s41598-018-22626-w

DO - 10.1038/s41598-018-22626-w

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VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 4534

ER -

Genetic Contributions to the Association between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis

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