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We aim to explore symptoms and symptom combinations associated with a subsequent cancer diagnosis and to establish their timeframe.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Using the QResearch Database, we carried out a matched nested case-control study. Associations between pre-specified symptoms encountered in primary care and a subsequent diagnosis of any cancer were explored using conditional logistic regression. Median diagnostic intervals were used to split symptoms into \u201clate\u201d and \u201cearly\u201d timeframes to identify relevant early symptoms.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>3186 cases and 50,576 controls were identified from a cohort of 3,424,771 CTYA. We identified 12 novel associations, of which hemiparesis [OR 90.9 (95%CI 24.7-335.1), PPV\u2009=\u20091.6%], testicular swelling [OR 186.7 (95%CI 86.1-404.8), PPV\u2009=\u20092.4%] and organomegaly [OR 221.6 (95%CI 28.3-1735.9), PPV\u2009=\u20095.4%] had significant positive predictive values (PPV). Limb pain, a known marker of serious illness in children, was a recurrent early symptom across cancer subtypes. Similar clinical presentations were observed across childhood and TYA cancers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Using the largest cohort to date, we provide novel information on the time-varying predictive utility of symptoms in the diagnosis of CTYA cancers. Our findings will help to raise clinical and public awareness of symptoms, stratify those at higher-risk and ultimately aid earlier diagnosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41416-024-02786-5","type":"journal-article","created":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T08:04:57Z","timestamp":1720944297000},"page":"1032-1042","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identifying early symptoms associated with a diagnosis of childhood, adolescent and young adult cancers: a population-based nested case-control study"],"prefix":"10.1038","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2414-2906","authenticated-orcid":false,"given":"D.","family":"Saatci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3467-6677","authenticated-orcid":false,"given":"J.","family":"Oke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Harnden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hippisley-Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,14]]},"reference":[{"key":"2786_CR1","unstructured":"Patel V https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/birthsdeathsandmarriages\/deaths\/bulletins\/childhoodinfantandperinatalmortalityinenglandandwales\/2017. 2019."},{"key":"2786_CR2","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/S1470-2045(19)30339-0","volume":"20","author":"Collaborators GBDCC.","year":"2019","unstructured":"Collaborators GBDCC. 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JHC is an unpaid director of QResearch, a not-for-profit organisation which is a partnership between the University of Oxford and EMIS Health who supply the QResearch database used for this work. Until 09 Aug 2023, JHC had a 50% shareholding in ClinRisk Ltd, co-owning it with her husband, who was an executive director. On 9th August 2023, 100% of the share capital was donated to Endeavour Health Care Charitable Trust and the company renamed to Endeavour Predict Ltd. JHC is an unpaid consultant to Endeavour Predict Ltd and her husband is a non-executive director to cover the transition. The company licences software both to the private sector and to NHS bodies or bodies that provide services to the NHS (through GP electronic health record providers, pharmacies, hospital providers and other NHS providers). This software implements algorithms (including QCancer) developed from access to the QResearch database during her time at the University of Nottingham. DS, JO, AH declare no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study protocol was approved by the QResearch Scientific Committee (reference OX94). The QResearch\u00ae ethics approval is with East Midlands-Derby Research Ethics Committee [reference 18\/EM\/0400]. The study used anonymised data from general practices contributing to QResearch on an individual \u2018opt-out\u2019 basis and therefore individual patient consent was not required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}