{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:07:34Z","timestamp":1789103254671,"version":"build-2803163510"},"reference-count":62,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Non-nutritive sweeteners (NNS) are chemical substances developed by the food industry to reduce sugar and calories while preserving sweetness. Epidemiological studies have indicated a potential increased risk of certain cancers, including breast cancer (BC), associated with NNS consumption. However, the evidence has exclusively relied on self-reported dietary information rather than objective measurements of NNSs. We examined the association of urinary concentrations of NNS with BC risk in women from the large Moli-sani Study. Methods: Using a case-cohort design, a sample of 988 middle-aged women (mean age 55 \u00b1 12 y) was randomly selected as a sub-cohort and compared to 272 women with incident BC (38 premenopausal and 234 postmenopausal). A total of 6 commonly used NNSs (i.e., aspartame, acesulfame, saccharin, sucralose, cyclamate, and steviol glycosides) were measured through liquid chromatography\u2013mass spectrometry in spot urine samples (creatinine-adjusted concentrations; \u00b5g\/mg) collected at baseline (2005\u20132010). The multivariable hazard ratios (HRs) were estimated using weighted Cox regression models for the case-cohort design, with each NNS modelled as a binary variable (i.e., presence vs. absence). The sum of these values produced a total urinary NNS score, which could range from 0 to 6, and was further categorised as low (0\u20131) or high (2\u20135). Results: The predominant NNS detected in urine was saccharin (E954), contributing to 77% of total NNSs, followed by steviol glycosides (E960;11%). In multivariable-adjusted Cox analyses, neither individual NNSs nor total NNS urinary concentrations were associated with overall BC risk (HR = 1.09; 95% CI 0.80\u20131.48 for high vs. low). However, the presence of sucralose (E955) was directly linked to premenopausal BC (HR = 5.90; 95% CI 1.44\u201324.20; p = 0.014), although this estimate was based on only 38 cases and was imprecise. Conclusions: Urinary NNS concentrations were not associated with overall BC risk. The observed association between urinary sucralose and premenopausal BC should be considered exploratory and hypothesis-generating and requires independent replication.<\/jats:p>","DOI":"10.3390\/nu18182958","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:26:11Z","timestamp":1788956771000},"page":"2958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary Concentrations of Non-Nutritive Sweeteners and Breast Cancer: A Case-Cohort Analysis of the Moli-sani Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8082-6552","authenticated-orcid":false,"given":"Marialaura","family":"Bonaccio","sequence":"first","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9767-7998","authenticated-orcid":false,"given":"Augusto","family":"Di Castelnuovo","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-1186","authenticated-orcid":false,"given":"Simona","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"},{"name":"Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, 21100 Varese, VA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8815-6170","authenticated-orcid":false,"given":"Claudia F.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7109-1128","authenticated-orcid":false,"given":"Emilia","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"},{"name":"Department of Medicine and Surgery, LUM University \u201cGiuseppe Degennaro\u201d, 70010 Casamassima, BA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Panzera","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Esposito","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"},{"name":"Department of Medicine and Surgery, LUM University \u201cGiuseppe Degennaro\u201d, 70010 Casamassima, BA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-0318","authenticated-orcid":false,"given":"Amalia","family":"De Curtis","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-040X","authenticated-orcid":false,"given":"Sara","family":"Magnacca","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-7379","authenticated-orcid":false,"given":"Jacopo","family":"Troisi","sequence":"additional","affiliation":[{"name":"Theoreo Srl, 84090 Montecorvino Pugliano, SA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4759-3179","authenticated-orcid":false,"given":"Chiara","family":"Cerletti","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Benedetta","family":"Donati","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7823-1402","authenticated-orcid":false,"given":"Giovanni","family":"de Gaetano","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0514-5885","authenticated-orcid":false,"given":"Licia","family":"Iacoviello","sequence":"additional","affiliation":[{"name":"Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, IS, Italy"},{"name":"Department of Medicine and Surgery, LUM University \u201cGiuseppe Degennaro\u201d, 70010 Casamassima, BA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","unstructured":"WHO (2026, September 03). 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