Investigating the relationship between taste perception of artificial sweeteners and cancer risk.

[OBJECTIVE] To investigate whether taste perception of two artificial sweeteners-aspartame and neohesperidin dihydrochalcone (NHDC)-is causally associated with the risk of site-specific cancers.

[DESIGN] A two-sample Mendelian randomisation (MR) study.

[SETTING] Genetic instruments for taste perception (6 for aspartame; 13 for NHDC) were obtained from a genome-wide association study (GWAS) of Australian adolescents, and cancer outcome data were sourced from publicly available GWAS datasets.

[PARTICIPANTS] Genetic data for taste perception from 1757 Australian adolescents and genetic data for cancers from large-scale GWAS cohorts, including UK Biobank ( 500 000) and FinnGen ( 500 000).

[RESULTS] A one sd increase in the genetically predicted perceived intensity of NHDC was associated with an increased risk of male genital cancer (OR = 1·11, 95 % CI: 1·04, 1·19) and prostate cancer (OR = 1·03, 95 % CI: 1·01, 1·08) based on FinnGen data. These associations persisted after multivariable MR adjustment for glucose and aspartame perception but were not replicated in the UK Biobank. A weak protective association between aspartame perception and cervical cancer (OR = 0·998, 95 % CI: 0·997, 0·999) was observed, but this attenuated to null in sensitivity analyses.

[CONCLUSIONS] This study found no compelling evidence that perception of aspartame or NHDC during adolescence causally influences later-life cancer risk. The findings highlight the importance of evaluating individual artificial sweeteners separately in future research examining potential health effects.