{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:08:05Z","timestamp":1784610485312,"version":"3.55.0"},"posted":{"date-parts":[[2025,4,24]]},"group-title":"Epidemiology","reference-count":81,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Early-onset bowel cancer incidence (age &lt;50 years) has increased worldwide and is highest in Australia, but how this varies across histology and anatomical site remains unclear. We aimed to investigate appendiceal, proximal colon, distal colon, rectal, and anal cancer incidence trends by age and histology in Australia.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Cancer incidence rate data were obtained from all Australian cancer registries (1990-2020 period). Birth cohort-specific incidence rate ratios (IRRs) and annual percentage change in rates were estimated using age-period-cohort modelling and joinpoint regression.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>After excluding neuroendocrine neoplasms, early-onset cancer incidence rose 5-9% annually, yielding 5,341 excess cases (2 per 100,000 person-years; 12% appendix, 45% colon, 36% rectum, 7% anus; 20-214% relative increase). Trends varied by site, period, and age: appendiceal cancer rose from 1990-2020 in 30-49-year-olds; colorectal cancers rose from around 1990-2010 in 20-29-year-olds and from 2010-2020 in 30-39-year-olds; anal cancer rose from 1990-2009 in 40-49-year-olds. Across all sites, IRRs increased with successive birth cohorts since 1960. Notably, adenocarcinoma incidence in the 1990s versus 1950s birth cohort was 2-3-fold for colorectum and 7-fold for appendix. The greatest subtype-specific increases occurred for appendiceal mucinous adenocarcinoma, colorectal non-mucinous adenocarcinoma, and anal squamous cell carcinoma. Only later-onset (age \u226550) colorectal and anal adenocarcinoma rates declined. Appendiceal tumours, neuroendocrine neoplasms (all sites), anorectal squamous cell carcinomas, and colon signet ring cell carcinomas rose across early-onset and later-onset strata.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>Appendiceal, colorectal, and anal cancer incidence is rising in Australia with variation across age and histology, underscoring the need to identify factors driving these trends.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>\n                    ALM is supported by an Australian Government Research Training Program Scholarship, Rowden White Scholarship, and WP Greene Scholarship. DDB is supported by a National Health and Medical Research Council of Australia (NHMRC) Investigator grant (GNT1194896), a University of Melbourne Dame Kate Campbell Fellowship, and by funding awarded to The Colon Cancer Family Registry (CCFR,\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.coloncfr.org\">www.coloncfr.org<\/jats:ext-link>\n                    ) from the National Cancer Institute (NCI), National Institutes of Health (NIH) [award U01 CA167551]. MAJ is supported by an NHMRC Investigator grant (GNT1195099), a University of Melbourne Dame Kate Campbell Fellowship, and by funding awarded to the CCFR from NCI, NIH [award U01 CA167551].\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.21.25326138","type":"posted-content","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T09:55:16Z","timestamp":1745488516000},"source":"Crossref","is-referenced-by-count":2,"title":["Age-specific trends in colorectal, appendiceal, and anal tumour incidence by histological subtype in Australia from 1990 to 2020: a population-based time-series analysis"],"prefix":"10.64898","author":[{"given":"Aaron L.","family":"Meyers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Dowty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Mahmood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finlay A.","family":"Macrae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Rosty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Buchanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025042610451349000_2025.04.21.25326138v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/CAAC.21834"},{"key":"2025042610451349000_2025.04.21.25326138v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00600-4"},{"issue":"1","key":"2025042610451349000_2025.04.21.25326138v1.3","first-page":"100065","article-title":"Early-onset colorectal cancer incidence in Norway: a national registry-based study (1993-2022) analyzing subsite and morphology trends","volume":"7","year":"2025","journal-title":"ESMO Gastrointestinal Oncology"},{"key":"2025042610451349000_2025.04.21.25326138v1.4","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-18-0523"},{"key":"2025042610451349000_2025.04.21.25326138v1.5","unstructured":"Australian Institute of Health and Welfare. 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