Urinary artificial sweeteners and breast cancer risk in women from the Moli-sani Study

Abstract Background Artificial sweeteners (AS) are chemical substances developed by the food industry to reduce sugar and calories while maintaining sweetness. Cohort studies suggested an increased risk of certain cancers, including breast cancer (BC), associated with AS intake, however evidence exclusively relied on self-reported dietary data rather than objectively measured AS. We examined the association of urinary biomarkers denoting AS intake with BC risk in women from the large Moli-sani Study. Methods Using a case-cohort design, a sample of 987 middle-aged women (mean age 55±12 y) was randomly selected as sub-cohort and compared with 273 women with incident BC (26 of them also belong to the sub-cohort). A total of 6 commonly used AS (i.e. aspartame, acesulfame, saccharine, sucralose, cyclamate, and steviol glycosides) were measured through liquid chromatography-mass spectrometry in urinary samples (creatinine-adjusted concentrations; µg/mg) collected at baseline (2005-2010). The multivariable hazard ratios (HRs) were estimated through Cox regression models using the Prentice method, where each AS was dichotomized as absence/presence, independent of concentrations. Results The main urinary AS was saccharine (E954), contributing to 71% of total AS, followed by steviol glycosides (E960;11%). During a median follow-up of 13.2 y we identified 38 premenopausal and 235 postmenopausal incident BC cases. In multivariable-adjusted Cox analyses, none of the individual AS was associated with overall BC risk, nor was the total urinary AS (HR = 0.93; 95%CI 0.63-1.37 for 1-unit increment). Compared to absence, presence of sucralose (E955) in urine was linked to premenopausal BC (HR = 4.23: 95%CI 1.23-14.51; p = 0.022). Conclusions Urinary artificial sweeteners were not associated with BC risk. However, sucralose presence in urine was linked to a higher risk of premenopausal BC. Prospective, dose-related studies with larger sample size are warranted to possibly confirm our findings. Key messages • The presence in the urine of commonly used artificial sweeteners was not associated with breast cancer risk. • Presence of urinary sucralose was linked to higher risk of premenopausal breast cancer.