{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:17:14Z","timestamp":1790785034898,"version":"4.1.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006667","name":"Ministry of National Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009309","name":"Northern Ireland Biobank","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009309","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015776","name":"Health and Social Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015776","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001626","name":"Development Division of the Public Health Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001626","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013311","name":"Northern Ireland and Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013311","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019154","name":"Belfast CRUK Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019154","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018383","name":"Northern Ireland Experimental Cancer Medicine Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018383","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015663","name":"Friends of the Cancer Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sean Crummey Foundation"},{"DOI":"10.13039\/100022943","name":"Northern Ireland Cancer Registry","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022943","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lifestyle factors such as smoking and alcohol may influence colon cancer (CC) survival, but it is unclear whether their effects vary by tumour-infiltrating immune biomarkers. This study examined CC-specific survival by smoking and alcohol status, stratified by immune cell density, in a large population-based cohort. The study included 661 individuals who underwent surgery for stage II or III CC between 2004 and 2008 within two Health and Social Care (HSC) Trusts in Northern Ireland. Representative formalin-fixed, paraffin-embedded (FFPE) tumour blocks were retrieved, and immunohistochemistry (IHC) was performed on tissue microarrays constructed from both the central tumour and the invasive margin. Cox proportional hazards models were used to assess CC-specific survival, adjusting for key clinical and demographic confounders. Ever smoking, compared to never smoking, was associated with poorer CC-specific survival among individuals with lower densities of CD3+, CD4 +, and FOXP3 + tumour-infiltrating immune cells. Among those with higher CD8 + cell density in the central tumour, ever smoking was linked to worse outcomes. Similar patterns were seen in the invasive margin, although these were not all statistically significant. No significant associations were observed between alcohol use and survival across any immune biomarker subgroups. Smoking was associated with poorer survival among patients with CC, and this association appears to be modified by the density of tumour-infiltrating immune cells.<\/jats:p>","DOI":"10.1093\/carcin\/bgag006","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:26:22Z","timestamp":1770035182000},"source":"Crossref","is-referenced-by-count":1,"title":["Smoking, alcohol, and colon cancer survival are modified by immune biomarkers: a population-representative study"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6314-4816","authenticated-orcid":false,"given":"Yasemin","family":"Adali","sequence":"first","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences, Centre for Public Health, Queen\u2019s University Belfast , Belfast BT12 6BA ,","place":["United Kingdom"]},{"name":"Department of Biophysics, Faculty of Medicine, Pamukkale University , Denizli 20160 ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-1765","authenticated-orcid":false,"given":"Maurice B","family":"Loughrey","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences, Centre for Public Health, Queen\u2019s University Belfast , Belfast BT12 6BA ,","place":["United Kingdom"]},{"name":"Patrick G Johnston Centre for Cancer Research, Queen\u2019s University , Belfast, Northern Ireland BT9 7AE ,","place":["United Kingdom"]},{"name":"Department of Cellular Pathology, Belfast Health and Social Care Trust , Belfast, Northern Ireland BT12 6BA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5476-751X","authenticated-orcid":false,"given":"Stephanie","family":"Craig","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen\u2019s University , Belfast, Northern Ireland BT9 7AE ,","place":["United Kingdom"]},{"name":"Precision Medicine Centre of Excellence, Queen\u2019s University Belfast , Northern Ireland BT9 7BL ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6592-5336","authenticated-orcid":false,"given":"Ronan T","family":"Gray","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences, Centre for Public Health, Queen\u2019s University Belfast , Belfast BT12 6BA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6945-6060","authenticated-orcid":false,"given":"Jacqueline A","family":"James","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen\u2019s University , Belfast, Northern Ireland BT9 7AE ,","place":["United Kingdom"]},{"name":"Precision Medicine Centre of Excellence, Queen\u2019s University Belfast , Northern Ireland BT9 7BL ,","place":["United Kingdom"]},{"name":"Northern Ireland Biobank, Queen\u2019s University Belfast , Northern Ireland BT9 7BL ,","place":["United Kingdom"]},{"name":"Regional Molecular Diagnostic Service, Belfast Health and Social Care Trust , Belfast, Northern Ireland BT12 6BA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8586-282X","authenticated-orcid":false,"given":"Manuel","family":"Salto-Tellez","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen\u2019s University , Belfast, Northern Ireland BT9 7AE ,","place":["United Kingdom"]},{"name":"Precision Medicine Centre of Excellence, Queen\u2019s University Belfast , Northern Ireland BT9 7BL ,","place":["United Kingdom"]},{"name":"Regional Molecular Diagnostic Service, Belfast Health and Social Care Trust , Belfast, Northern Ireland BT12 6BA ,","place":["United Kingdom"]},{"name":"Integrated Pathology Unit, Institute of Cancer Research , London SW7 3RP ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9160-283X","authenticated-orcid":false,"given":"Philip D","family":"Dunne","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen\u2019s University , Belfast, Northern Ireland BT9 7AE ,","place":["United Kingdom"]},{"name":"CRUK Scotland Institute , Glasgow G61 1BD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4872-7877","authenticated-orcid":false,"given":"Helen G","family":"Coleman","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences, Centre for Public Health, Queen\u2019s University Belfast , Belfast BT12 6BA ,","place":["United Kingdom"]},{"name":"Patrick G Johnston Centre for Cancer Research, Queen\u2019s University , Belfast, Northern Ireland BT9 7AE ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"2026030413262564000_bgag006-B1","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1517\/17530059.1.4.439","article-title":"Immunologic markers of cancer progression and prognosis","volume":"1","author":"Singhal","year":"2007","journal-title":"Expert Opin Med Diagn"},{"key":"2026030413262564000_bgag006-B2","doi-asserted-by":"publisher","first-page":"622","DOI":"10.3389\/fimmu.2019.00622","article-title":"Double positive CD4","volume":"10","author":"Bohner","year":"2019","journal-title":"Front Immunol"},{"key":"2026030413262564000_bgag006-B3","doi-asserted-by":"publisher","first-page":"172","DOI":"10.4161\/onci.1.2.18311","article-title":"A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth","volume":"1","author":"Wen","year":"2012","journal-title":"Oncoimmunology"},{"key":"2026030413262564000_bgag006-B4","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nrc3245","article-title":"The immune contexture in human tumours: impact on clinical outcome","volume":"12","author":"Fridman","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"2026030413262564000_bgag006-B5","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/bjc.2011.189","article-title":"The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis","volume":"105","author":"Gooden","year":"2011","journal-title":"Br J Cancer"},{"key":"2026030413262564000_bgag006-B6","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/S2468-1253(24)00091-8","article-title":"Clinical significance of combined tumour-infiltrating lymphocytes and microsatellite instability status in colorectal cancer: a systematic review and network meta-analysis","volume":"9","author":"Wankhede","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026030413262564000_bgag006-B7","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.bpg.2017.09.015","article-title":"Do smoking and alcohol behaviours influence GI cancer survival?","volume":"31","author":"McMenamin","year":"2017","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"2026030413262564000_bgag006-B8","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1097\/CJI.0b013e3181d32f01","article-title":"Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy","volume":"33","author":"Correale","year":"2010","journal-title":"J Immunother"},{"key":"2026030413262564000_bgag006-B9","doi-asserted-by":"publisher","first-page":"e91","DOI":"10.1038\/CTG.2017.18","article-title":"Evaluation of PTGS2 expression, PIK3CA mutation, aspirin use and colon cancer survival in a population-based cohort study","volume":"8","author":"Gray","year":"2017","journal-title":"Clin Transl Gastroenterol"},{"key":"2026030413262564000_bgag006-B10","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.gastha.2022.11.005","article-title":"Distinct molecular profiles of sporadic early-onset colorectal cancer: a population-based cohort and systematic review","volume":"2","author":"Hamilton","year":"2022","journal-title":"Gastro Hep Adv"},{"key":"2026030413262564000_bgag006-B11","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1038\/bjc.2017.139","article-title":"Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study","volume":"116","author":"Gray","year":"2017","journal-title":"Br J Cancer"},{"key":"2026030413262564000_bgag006-B12","doi-asserted-by":"publisher","DOI":"10.5334\/OJB.47","article-title":"The Northern Ireland Biobank","volume":"5","author":"Lewis","year":"2018","journal-title":"Open J Bioresour"},{"key":"2026030413262564000_bgag006-B13","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/his.13516","article-title":"Validation of the systematic scoring of immunohistochemically stained tumour tissue microarrays using QuPath digital image analysis","volume":"73","author":"Loughrey","year":"2018","journal-title":"Histopathology"},{"key":"2026030413262564000_bgag006-B14","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1038\/s41416-020-0985-5","article-title":"Immune status is prognostic for poor survival in colorectal cancer patients and is associated with tumour hypoxia","volume":"123","author":"Craig","year":"2020","journal-title":"Br J Cancer"},{"key":"2026030413262564000_bgag006-B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41416-020-0985-5","article-title":"Qupath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"2026030413262564000_bgag006-B16","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.1038\/s41598-020-60255-4","article-title":"The prognostic implications of tumor infiltrating lymphocytes in colorectal cancer: a systematic review and meta-analysis","volume":"10","author":"Idos","year":"2020","journal-title":"Sci Rep"},{"key":"2026030413262564000_bgag006-B17","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1093\/jnci\/djy137","article-title":"Smoking and risk of colorectal cancer sub-classified by tumor-infiltrating T cells","volume":"111","author":"Hamada","year":"2019","journal-title":"J Natl Cancer Inst"},{"key":"2026030413262564000_bgag006-B18","doi-asserted-by":"publisher","first-page":"268","DOI":"10.18632\/oncotarget.13613","article-title":"Impacts of cigarette smoking on immune responsiveness: up and down or upside down?","volume":"8","author":"Qiu","year":"2017","journal-title":"Oncotarget"},{"key":"2026030413262564000_bgag006-B19","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3390\/biom7030061","article-title":"Alcohol and cancer: mechanisms and therapies","volume":"7","author":"Ratna","year":"2017","journal-title":"Biomolecules"},{"key":"2026030413262564000_bgag006-B20","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1159\/000107679","article-title":"Changes in the immune system after moderate beer consumption","volume":"51","author":"Romeo","year":"2007","journal-title":"Ann Nutr Metab"},{"key":"2026030413262564000_bgag006-B21","doi-asserted-by":"publisher","first-page":"104098","DOI":"10.1016\/j.labinv.2025.104098","article-title":"Virtual tissue microarrays for validating digital biomarker analysis in colorectal carcinomaf","volume":"105","author":"J\u00f8rgensen","year":"2025","journal-title":"Lab Invest"},{"key":"2026030413262564000_bgag006-B22","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1097\/PAI.0000000000001266","article-title":"Immune profiling of incidental NSCLC patients: comparison between tumor sections and TMA cores","volume":"33","author":"Caminha","year":"2025","journal-title":"Appl Immunohistochem Mol Morphol"}],"container-title":["Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/carcin\/advance-article-pdf\/doi\/10.1093\/carcin\/bgag006\/66725690\/bgag006.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/carcin\/article-pdf\/47\/1\/bgag006\/66725690\/bgag006.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/carcin\/article-pdf\/47\/1\/bgag006\/66725690\/bgag006.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:26:34Z","timestamp":1772648794000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/carcin\/article\/doi\/10.1093\/carcin\/bgag006\/8456295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12,26]]}},"URL":"https:\/\/doi.org\/10.1093\/carcin\/bgag006","relation":{},"ISSN":["0143-3334","1460-2180"],"issn-type":[{"value":"0143-3334","type":"print"},{"value":"1460-2180","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2025,12,26]]},"article-number":"bgag006"}}