{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:47:35Z","timestamp":1791953255826,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Prospective studies have reported associations between systemic inflammatory biomarkers and colorectal cancer (CRC) risk, but whether these reflect a causal role of inflammation or responses to preclinical disease remains uncertain. Methods: Using data from 383,850 UK Biobank participants (aged 40\u201369 years; recruited 2006\u20132010), we investigated potential reverse causality by assessing these associations according to time since biomarker assessment. Baseline systemic inflammatory markers, including C-reactive protein (CRP), albumin, and blood cell-derived ratios, were assessed. Multivariable Cox models estimated associations with CRC risk across predefined follow-up intervals. Results: Over a median follow-up of 11.8 years, 4996 participants developed CRC. Inflammatory biomarkers were associated with increased CRC risk, particularly during the early follow-up. Associations weakened substantially or disappeared when early follow-up was excluded. For example, CRP was associated with a 3.03-fold higher CRC risk (highest vs. lowest quartile; 95% CI: 2.06\u20134.45) within the 0\u20131-year interval, while no association was observed during the 3\u20135, 6\u20138, or &gt;8-year intervals. Across complete follow-up, the association remained statistically significant but much weaker (HR: 1.17; 95% CI: 1.07\u20131.28). Similar patterns were observed for most other biomarkers, except the platelet-to-neutrophil ratio. Conclusions: Our results suggest that the associations between inflammatory biomarkers and CRC risk may partly reflect reverse causality arising from preclinical disease.<\/jats:p>","DOI":"10.3390\/cancers18193190","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:50:38Z","timestamp":1790959838000},"page":"3190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Inflammation and Colorectal Cancer: Assessing the Role of Reverse Causality"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3293-9499","authenticated-orcid":false,"given":"Fatemeh","family":"Safizadeh","sequence":"first","affiliation":[{"name":"Cancer Prevention Graduate School, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5683-6315","authenticated-orcid":false,"given":"Tafirenyika","family":"Gwenzi","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7372-8284","authenticated-orcid":false,"given":"Marko","family":"Mandic","sequence":"additional","affiliation":[{"name":"Cancer Prevention Graduate School, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hoffmeister","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology of Early Cancer Detection, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-1572","authenticated-orcid":false,"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"Cancer Prevention Graduate School, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103177","DOI":"10.1016\/j.critrevonc.2020.103177","article-title":"Chronic inflammation towards cancer incidence: A systematic review and meta-analysis of epidemiological studies","volume":"157","author":"Michels","year":"2021","journal-title":"Crit. 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