{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:15:48Z","timestamp":1778066148933,"version":"3.51.4"},"reference-count":59,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Dose-Response"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The long-term biological effects of low-level exposure to artificial sweeteners remain debated. We integrated computational toxicology and Mendelian randomization (MR) to explore potential biological responses associated with sodium saccharin across multiple cancer outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Public databases were screened to identify saccharin-related targets, followed by protein\u2013protein interaction network construction and enrichment analyses. Molecular docking assessed binding potential. Two-sample MR analyses were conducted using European genome-wide association study (GWAS) summary statistics to evaluate potential causal associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 191 identified targets, 160 overlapped with genes implicated across 36 cancer types. Hub genes included\n                      <jats:italic toggle=\"yes\">TP53, IL6, and MAPK3<\/jats:italic>\n                      , with docking indicating moderate binding affinity. Enrichment analyses highlighted inflammatory pathways including interleukin-17 signaling. MR analyses suggested inverse associations with non-melanoma skin cancer (odds ratio [OR] = 0.38,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.006) and colon cancer (OR = 0.56,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), while a preliminary positive signal was observed for Kaposi sarcoma (OR = 3.73,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.044). No significant associations were detected for most other cancers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sodium saccharin may interact with cancer-related molecular networks; however, population-level evidence indicates heterogeneous and context-dependent associations rather than a generalized carcinogenic effect under low-level exposure conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15593258261446844","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:51:21Z","timestamp":1777859481000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterogeneous Biological Responses to Low-Level Sodium Saccharin Exposure: An Integrated Computational Toxicology and Mendelian Randomization 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