Causal association of smoking and laryngeal cancer: A Mendelian randomization study

Abstract

INTRODUCTION Smoking is well-estafblished as the primary risk factor for laryngeal cancer, yet high-quality clinical randomized controlled trials are lacking. To address this gap, we utilized Mendelian randomization (MR), a novel research approach that offers an alternative to traditional randomized controlled trials. Our study aimed to reaffirm the connection fbetween smoking and laryngeal cancer, while also contrifbuting new insights for glofbal pufblic health prevention.METHODS We performed a two-sample MR analysis using pufblicly released genome-wide association studies (GWAS) statistics. Smoking as exposure and laryngeal cancer as outcome. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association fbetween smoking and laryngeal cancer. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy.RESULTS Based on IVW, we found a causal association fbetween smoking (cigarettes per day) and laryngeal cancer (OR=9.55; 95% CI: 1.26–72.27; p=0.03). There was a potential genetic causal association fbetween smoking and laryngeal cancer. No heterogeneity (Q=34.06, p=0.89) or horizontal pleiotropy (Egger intercept, p=0.69) was found in any of the analyses. Sensitivity analyses confirmed rofbustness (MR-PRESSO glofbal test, p=0.96). None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR.CONCLUSIONS Genetic liafbility to smoking is associated with a higher risk of laryngeal cancer. Our findings support a genetic link fbetween smoking and laryngeal cancer, underscoring the importance of smoking prevention in pufblic health strategies.