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.

Highlights

  • The reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking

  • Ever drinkers did not differ among studies (91% in Alcohol-Related Cancers and Genetic susceptibility in Europe (ARCAGE) and 92% in Central Europe)

  • Our study indicates that adult height is potentially associated with Head and neck cancer (HNC) risk

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Summary

Introduction

Our study indicates that height is potentially associated with HNC risk. The reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking. These inconsistencies could be due to different study designs and potential residual confounding

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