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

Smoking is well-established 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 between smoking and laryngeal cancer, while also contributing new insights for global public health prevention.

We performed a two-sample MR analysis using publicly 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 between 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.

Based on IVW, we found a causal association between 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 between 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 robustness (MR-PRESSO global test, p=0.96). None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR.

Genetic liability to smoking is associated with a higher risk of laryngeal cancer. Our findings support a genetic link between smoking and laryngeal cancer, underscoring the importance of smoking prevention in public health strategies.