Causal impact of air pollution on head and neck cancer: a Mendelian randomization study

Exposure to air pollutants is a significant global health concern linked to numerous diseases. However, the causal role of air pollution in the development of head and neck cancer (HNC) remains uncertain.

To investigate this relationship, we employed two-sample Mendelian randomization (TSMR), MRlap, and multivariable Mendelian randomization (MVMR) analyses using publicly available genome-wide association study (GWAS) datasets. Additionally, we explored potential mediating proteins and underlying biological mechanisms.

Our findings revealed a significant causal association between nitrogen dioxide (NO₂) exposure and increased risk of HNC (odds ratio [OR] = 1.008, 95% confidence interval [CI]: 1.001-1.016, P = 0.036), as well as between nitrogen oxides (NOₓ) and HNC (OR = 1.010, 95% CI: 1.003-1.018, P = 0.005). Specifically, NOₓ exposure was causally linked to oral and oropharyngeal cancers (OR = 1.009, 95% CI: 1.003-1.016, P = 0.007). These associations were supported by sensitivity analyses, pleiotropy assessments, MRlap, and MVMR approaches. Furthermore, sushi domain-containing protein 2 (SUSD2) and bactericidal permeability-increasing protein (BPI) were identified as potential mediators, and protein methylation was identified as a plausible underlying mechanism linking air pollutant exposure with HNC.

Exposure to NO₂ and NO_x air pollutants is causally associated with an elevated risk of developing HNC. Reducing exposure to these pollutants may be an effective strategy for decreasing the incidence of HNC.