{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:51:12Z","timestamp":1790268672866,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872702"],"award-info":[{"award-number":["81872702"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003534"],"award-info":[{"award-number":["82003534"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20200674"],"award-info":[{"award-number":["BK20200674"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastrointestinal (GI) cancer risk has been associated with metabolic syndrome (MetS), a surrogate indicator for unhealthy lifestyles, and a number of genetic loci, but the combined effect of MetS and genetic variants on GI cancer risk is uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 430,036 participants with available MetS and genotype data from UK Biobank. During the follow\u2010up time, 5494 incident GI cancer cases, including esophageal cancer, gastric cancer, and colorectal cancer, were identified. We created a GI polygenic risk score (GI\u2010PRS) for overall GI cancer derived from three site\u2010specific cancer PRSs. Cox proportional hazards regression was used to estimate the associations of MetS and GI\u2010PRS with the risk of GI cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MetS was significantly associated with 28% increment in GI cancer risk (hazard ratio [HR]\n                      <jats:sub>MetS vs. non\u2010MetS<\/jats:sub>\n                      : 1.28, 95% confidence interval [CI]: 1.21\u20131.35,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), whereas a high GI\u2010PRS (top quintile) was associated with 2.28\u2010fold increase in risk (HR\n                      <jats:sub>high vs. low<\/jats:sub>\n                      : 2.28, 95% CI: 2.09\u20132.49,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Compared with participants without MetS and at low genetic risk (bottom quintile of GI\u2010PRS), those with MetS and at high genetic risk had 2.75\u2010fold increase in GI cancer risk (HR: 2.75, 95% CI: 2.43\u20133.12,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Additionally, MetS in comparison with no MetS had 1.49\u2030, 2.75\u2030, and 3.37\u2030 absolute risk increases in 5\u2009years among participants at low, intermediate (quintiles 2\u20134 of GI\u2010PRS) and high genetic risk, respectively, representing the number of subjects diagnosed as MetS causing a new GI cancer case in 5\u2009years were 669, 364, and 296, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Metabolic and genetic factors may jointly contribute to GI cancer risk and may serve as predictors by quantitative measurements to identify high\u2010risk populations of GI cancer for precise prevention.<\/jats:p>\n                  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Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Digestive Endoscopy Department and General Surgery Department The First Affiliated Hospital with Nanjing Medical University and Jiangsu Province Hospital  Nanjing 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 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