{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:18:40Z","timestamp":1793409520308,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Center for Administrative Data Research"},{"name":"Washington University Institute of Clinical and Translational Sciences","award":["UL1 TR002345"],"award-info":[{"award-number":["UL1 TR002345"]}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32 DK007130"],"award-info":[{"award-number":["T32 DK007130"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32 CA009621"],"award-info":[{"award-number":["T32 CA009621"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NOD","award":["P30 DK52574"],"award-info":[{"award-number":["P30 DK52574"]}]},{"name":"NOD","award":["R37 CA246175"],"award-info":[{"award-number":["R37 CA246175"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18-64 years) with 2\u2009or more years of continuous enrollment (2006-2015) to identify red-flag signs and symptoms between 3\u2009months to 2\u2009years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3\u2009months of diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between 3\u2009months and 2\u2009years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (Ptrend\u2009&amp;lt;\u2009.001), respectively, with stronger associations for younger ages (Pinteraction\u2009&amp;lt;\u2009.001) and rectal cancer (Pheterogenity\u2009=\u2009.012). The number of different signs and symptoms was predictive of early-onset CRC beginning 18\u2009months before diagnosis. Approximately 19.3% of patients had their first sign or symptom occur between 3\u2009months and 2\u2009years before diagnosis (median diagnostic interval = 8.7\u2009months), and approximately 49.3% had the first sign or symptom within 3\u2009months of diagnosis (median diagnostic interval = 0.53\u2009month).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djad068","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:26:59Z","timestamp":1683160019000},"page":"909-916","source":"Crossref","is-referenced-by-count":90,"title":["Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer"],"prefix":"10.1093","volume":"115","author":[{"given":"Cassandra D L","family":"Fritz","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5403-3615","authenticated-orcid":false,"given":"Ebunoluwa E","family":"Otegbeye","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5646-710X","authenticated-orcid":false,"given":"Xiaoyu","family":"Zong","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Demb","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of California San Diego , San Diego, CA, USA"},{"name":"Moores Cancer Center, University of California San Diego , La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4116-512X","authenticated-orcid":false,"given":"Katelin B","family":"Nickel","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A","family":"Olsen","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine , St. Louis, MO, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Mutch","sequence":"additional","affiliation":[{"name":"Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas O","family":"Davidson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of California San Diego , San Diego, CA, USA"},{"name":"Moores Cancer Center, University of California San Diego , La Jolla, CA, USA"},{"name":"Department of Internal Medicine, University of California San Diego , San Diego, CA, USA"},{"name":"Veteran Affairs San Diego Healthcare System, Department of Medicine, Division of Gastroenterology , San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9835-7662","authenticated-orcid":false,"given":"Yin","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine , St. Louis, MO, USA"},{"name":"Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine , St. Louis, MO, USA"},{"name":"Alvin J. 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