Artificial sweetener and respiratory system cancer: A Mendelian randomization analysis.

Background & Aims: The association between artificial sweeteners and various cancers has been investigated, but their relationship with respiratory system cancers remains uncertain. To address this knowledge gap, we conducted a comprehensive Mendelian Randomization (MR) analysis.

Methods: We looked for SNPs associated with artificial sweetener intake and respiratory system cancers from the IEU OpenGWAS project, as well as SNPs related to sweet taste in artificial sweeteners from Hwang et al.'s study. Rigorous quality control procedures were implemented to select instrumental Single Nucleotide Polymorphisms that were closely linked to artificial sweetener intake. To ensure the reliability of our findings, we employed five different analytical methods, with the inverse variance weighting method being the primary approach. Additionally, we thoroughly assessed heterogeneity, pleiotropy, and sensitivity. Finally, we conducted Multivariable Mendelian Randomization (MVMR) to validate our results.

Results: Intake of artificial sweetener added to cereal showed a positive association with malignant neoplasm of the lip, oral cavity, and pharynx (OR: 1027.54; 95% CI: 4.8-219994.46; P = 0.011), and the result was also confirmed by the MVMR analysis. In addition, better perceived intensity of aspartame was negatively associated with cancers in these regions (OR: 0.49; 95% CI: 0.28-0.88; P = 0.016). Intake of artificial sweetener added to coffee or tea was not related with respiratory system cancer.

Conclusions: Our research offers evidence that the consumption of artificial sweeteners in cereals could increase the risk of cancers in the lip, oral cavity, and pharynx. Additionally, a greater sensitivity to the taste of aspartame may lower this risk.