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However, the nature of this association remains uncertain due to confounding factors, reverse causation, and biases inherent in observational research. To address this gap, we conducted a two-sample Mendelian randomization (MR) study to assess the causal relationship between T1D and 22 site-specific cancers. Using summary statistics from large-scale genome-wide association studies of European ancestry, comprising data on T1D (N\u2009=\u2009520,580) and the 22 site-specific cancers, we selected single nucleotide polymorphisms strongly associated with T1D as instruments for our analysis. Causal relationships were primarily evaluated through inverse-variance weighting-based analyses, supplemented by three additional methods: MR-Egger, weighted median, and mode-based estimate. Sensitivity analyses were performed, excluding genetic variants with potential pleiotropic effects. The finding demonstrated a causal association between T1D and increased risks of lung cancer (OR\u2009=\u20091.018, 95% CI 1.004\u20131.033, <jats:italic>p<\/jats:italic>\u2009=\u20090.011), colorectal cancer (OR\u2009=\u20091.022, 95% CI 1.003\u20131.041, <jats:italic>p<\/jats:italic>\u2009=\u20090.019), and prostate cancer (OR\u2009=\u20091.018, 95% CI 1.005\u20131.030, <jats:italic>p<\/jats:italic>\u2009=\u20090.006). Conversely, T1D was associated with decreased risks of breast cancer (OR\u2009=\u20090.989, 95% CI 0.981\u20130.998, <jats:italic>p<\/jats:italic>\u2009=\u20090.016), lymphoma (OR\u2009=\u20090.999, 95% CI 0.974\u20130.999, <jats:italic>p<\/jats:italic>\u2009=\u20090.003), malignant melanoma (OR\u2009=\u20090.999, 95% CI 0.989\u20130.999, <jats:italic>p<\/jats:italic>\u2009=\u20090.001), and non-melanoma skin cancer (OR\u2009=\u20090.999, 95% CI 0.899\u20130.999, <jats:italic>p<\/jats:italic>\u2009=\u20090.003). Our MR study provides an evidence of causal association between T1D and altered risks of various site-specific cancers. Further research is recommended to validate this finding in diverse populations to enhance the generalizability of findings across different ethnic groups.<\/jats:p>","DOI":"10.1038\/s41598-025-89288-3","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T20:13:24Z","timestamp":1743797604000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A two-sample Mendelian randomization study of type 1 diabetes and the risk of 22 site-specific cancers"],"prefix":"10.1038","volume":"15","author":[{"given":"Mikiyas Amare","family":"Getu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianbin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"issue":"10394","key":"89288_CR1","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1016\/S0140-6736(23)00223-4","volume":"401","author":"T Quattrin","year":"2023","unstructured":"Quattrin, T., Mastrandrea, L. 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