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We identified 25,887 participants with T2D by clinical data, baseline self\u2010report data, and biochemistry data. HbA1c and random blood glucose were measured at baseline. The associations of T2D, HbA1c, and random blood glucose with the risk of overall cancer and 20 site\u2010specific cancers, stratified by gender, were evaluated by the Cox regression models. We calculated the cancer site\u2010specific polygenic risk scores (PRS) to define genetic risk for each cancer and evaluated the joint effects of genetic risk and T2D on cancer risk. Additive and multiplicative interaction models were established to assess the gene\u2010T2D interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During a median follow\u2010up of 10.95\u2009years, 41,650 incident cancer cases were observed, including 21,957 males and 19,693 females. For all cancers combined, a higher risk was found in females with T2D (HR: 1.20, 95% CI: 1.13\u20131.28) or high HbA1c levels (\u2265\u200948\u2009mmol\/mol) (HR: 1.20, 95% CI: 1.10\u20131.31). Among site\u2010specific cancers, individuals with T2D or high glycemic traits had a higher risk of pancreatic, bladder, kidney, colorectal, gastric, lung and endometrial cancer. In contrast, we observed inverse associations of T2D and glycemic traits with prostate cancer. Additive interactions between high PRS and T2D were observed in pancreatic cancer risk (with relative excess risk of interaction (RERI) of 2.39 (95% CI: 0.34 to 4.72) and 4.41 (95% CI: 1.09 to 8.62), in males and females respectively), and in prostate cancer risk (with RERI of \u22120.94 (95% CI: \u22121.51 to \u22120.37) in males).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study suggests that T2D and high glycemic traits are associated with a higher risk of multiple malignant cancers, particularly in females.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71929","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T04:29:49Z","timestamp":1779078589000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Type 2 Diabetes, Glycemic Traits and Overall Cancer Risk: A Large\u2010Scale Prospective Cohort Study"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0821-4079","authenticated-orcid":false,"given":"Aiping","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Affiliated Hospital of Yangzhou University, Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing Jiangsu 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University  Nanjing Jiangsu China"},{"name":"The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi People's Hospital Nanjing Medical University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0249-5337","authenticated-orcid":false,"given":"Guangfu","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Sir Run Run Hospital Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Affiliated Hospital of Yangzhou University, Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Affiliated Hospital of Yangzhou University, Yangzhou University  Yangzhou Jiangsu 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