{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:55:14Z","timestamp":1792670114700,"version":"4.5.0"},"reference-count":50,"publisher":"Harborside Press, LLC","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>The aim of this study was to explore the risk of invasive colorectal cancer (CRC) in relatives of patients with colorectal carcinoma in situ (CCIS), which is lacking in the literature.<jats:bold>Patients and Methods:<\/jats:bold>We collected data from Swedish family-cancer datasets and calculated standardized incidence ratio (SIR) and cumulative risk of CRC in family histories of CCIS in first- and second-degree relatives. Family history was defined as a dynamic (time-dependent) variable allowing for changes during the follow-up period from 1958 to 2015. Of 12,829,251 individuals with available genealogical data, 173,796 were diagnosed with CRC and 40,558 with CCIS.<jats:bold>Results:<\/jats:bold>The lifetime (0\u201379 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5\u20131.7; n=752) increased risk. A similarly increased lifetime cumulative risk (6.7%) was found among first-degree relatives of patients with CRC (SIR, 1.6; 95% CI, 1.6\u20131.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1\u20133.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3\u20132.1; n=78). Moreover, the increased risk of CRC was higher for younger age at diagnosis of CCIS in the affected first-degree relative and for younger age at diagnosis of CRC in the index person.<jats:bold>Conclusions:<\/jats:bold>Results of this study show that first-degree relatives and half-siblings of patients with CCIS have an increased risk of CRC, which is comparable in magnitude to the risk of those with a family history of invasive CRC. These findings extend available evidence on familial risk of CRC and may help to refine guidelines and recommendations for CRC screening.<\/jats:p>","DOI":"10.6004\/jnccn.2021.7004","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T16:24:33Z","timestamp":1633105473000},"page":"1252-1257","source":"Crossref","is-referenced-by-count":7,"title":["Importance of Family History of Colorectal Carcinoma In Situ Versus Invasive Colorectal Cancer: A Nationwide Cohort Study"],"prefix":"10.6004","volume":"19","author":[{"given":"Yu","family":"Tian","sequence":"first","affiliation":[{"name":"1Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), and"},{"name":"2Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany;"},{"name":"3School of Public Health, Capital Medical University, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Kharazmi","sequence":"additional","affiliation":[{"name":"1Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), and"},{"name":"4Center for Primary Health Care Research, Lund University, Malm\u00f6, Sweden;"},{"name":"5Statistical Genetics Group, Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"1Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), and"},{"name":"6Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany;"},{"name":"7German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Xu","sequence":"additional","affiliation":[{"name":"1Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), and"},{"name":"2Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Sundquist","sequence":"additional","affiliation":[{"name":"4Center for Primary Health Care Research, Lund University, Malm\u00f6, Sweden;"},{"name":"8Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York;"},{"name":"9Center for Community-based Healthcare Research and Education, Department of Functional Pathology, School of Medicine, Shimane University, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sundquist","sequence":"additional","affiliation":[{"name":"4Center for Primary Health Care Research, Lund University, Malm\u00f6, Sweden;"},{"name":"8Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York;"},{"name":"9Center for Community-based Healthcare Research and Education, Department of Functional Pathology, School of Medicine, Shimane University, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Fallah","sequence":"additional","affiliation":[{"name":"1Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), and"},{"name":"4Center for Primary Health Care Research, Lund University, Malm\u00f6, Sweden;"},{"name":"10Department of Global Public Health and Primary Care, Faculty of Medicine, University of Bergen, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"ref511","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1053\/j.gastro.2016.01.015","article-title":"Family history of colorectal adenomas: taking the methodological bull by the horns","volume":"150","author":"Kahi","year":"2016","journal-title":"Gastroenterology"},{"key":"ref271","first-page":"660","article-title":"Reliability in the classification of advanced colorectal adenomas","volume":"11","author":"Terry","year":"2002","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"djw322","DOI":"10.1093\/jnci\/djw322","article-title":"Colorectal cancer incidence patterns in the United States, 1974\u20132013","volume":"109","author":"Siegel","year":"2017","journal-title":"J Natl Cancer Inst"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1053\/j.gastro.2020.03.063","article-title":"Calculating starting age for screening in relatives of patients with colorectal cancer based on data from large nationwide datasets","volume":"159","author":"Tian","year":"2020","journal-title":"Gastroenterology"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1002\/ijc.24795","article-title":"The Swedish Family-Cancer Database 2009: prospects for histology-specific and immigrant studies","volume":"126","author":"Hemminki","year":"2010","journal-title":"Int J Cancer"},{"key":"ref451","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.gie.2020.01.014","article-title":"Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer","volume":"91","author":"Gupta","year":"2020","journal-title":"Gastrointest Endosc"},{"key":"ref521","first-page":"41","article-title":"Invasive carcinomas may arise in colorectal adenomas with high-grade dysplasia and with carcinoma in situ","volume":"3","author":"Rubio","year":"2010","journal-title":"Int J Clin Exp Med"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/ajg.2017.174","article-title":"colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer","volume":"112","author":"Rex","year":"2017","journal-title":"Am J Gastroenterol"},{"key":"ref251","first-page":"19","article-title":"Genetic alterations in colorectal cancer","volume":"5","author":"Armaghany","year":"2012","journal-title":"Gastrointest Cancer Res"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"ref491","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/ajg.2017.174","article-title":"colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer","volume":"112","author":"Rex","year":"2017","journal-title":"Am J Gastroenterol"},{"key":"ref311","first-page":"153","article-title":"Colorectal carcinoma: pathologic aspects","volume":"3","author":"Fleming","year":"2012","journal-title":"J Gastrointest Oncol"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"311","DOI":"10.14309\/ajg.0000000000000467","article-title":"Advanced colorectal polyps on colonoscopy: a trigger for earlier screening of family members","volume":"115","author":"Molmenti","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ejca.2005.09.023","article-title":"Relative and absolute risk of colorectal cancer for individuals with a family history: a meta-analysis","volume":"42","author":"Butterworth","year":"2006","journal-title":"Eur J Cancer"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1136\/gutjnl-2019-319511","article-title":"Global patterns and trends in colorectal cancer incidence in young adults","volume":"68","author":"Siegel","year":"2019","journal-title":"Gut"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/02841860802247664","article-title":"The completeness of the Swedish Cancer Register: a sample survey for year 1998","volume":"48","author":"Barlow","year":"2009","journal-title":"Acta Oncol"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"12891","DOI":"10.1038\/srep12891","article-title":"Population landscape of familial cancer","volume":"5","author":"Frank","year":"2015","journal-title":"Sci Rep"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"836","DOI":"10.7326\/0003-4819-119-8-199310150-00010","article-title":"Polyp guideline: diagnosis, treatment, and surveillance for patients with nonfamilial colorectal polyps. The Practice Parameters Committee of the American College of Gastroenterology","volume":"119","author":"Bond","year":"1993","journal-title":"Ann Intern Med"},{"key":"ref11","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-40618-3","volume-title":"AJCC Cancer Staging Manual","author":"Amin","year":"2017"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"980","DOI":"10.14309\/ajg.0000000000000639","article-title":"Increased risk of colorectal cancer tied to advanced colorectal polyps: an untapped opportunity to screen first-degree relatives and decrease cancer burden","volume":"115","author":"Kolb","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"ref551","first-page":"660","article-title":"Reliability in the classification of advanced colorectal adenomas","volume":"11","author":"Terry","year":"2002","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref531","first-page":"19","article-title":"Genetic alterations in colorectal cancer","volume":"5","author":"Armaghany","year":"2012","journal-title":"Gastrointest Cancer Res"},{"key":"ref161","first-page":"865","article-title":"Familial risks in in situ cancers from the Family-Cancer Database","volume":"7","author":"Hemminki","year":"1998","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"l803","DOI":"10.1136\/bmj.l803","article-title":"Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study","volume":"364","author":"Tian","year":"2019","journal-title":"BMJ"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1002\/ijc.24795","article-title":"The Swedish Family-Cancer Database 2009: prospects for histology-specific and immigrant studies","volume":"126","author":"Hemminki","year":"2010","journal-title":"Int J Cancer"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"311","DOI":"10.14309\/ajg.0000000000000467","article-title":"Advanced colorectal polyps on colonoscopy: a trigger for earlier screening of family members","volume":"115","author":"Molmenti","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/02841860802247664","article-title":"The completeness of the Swedish Cancer Register: a sample survey for year 1998","volume":"48","author":"Barlow","year":"2009","journal-title":"Acta Oncol"},{"key":"ref31","first-page":"153","article-title":"Colorectal carcinoma: pathologic aspects","volume":"3","author":"Fleming","year":"2012","journal-title":"J Gastrointest Oncol"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"e8076","DOI":"10.1136\/bmj.e8076","article-title":"Familial risk of early and late onset cancer: nationwide prospective cohort study","volume":"345","author":"Kharazmi","year":"2012","journal-title":"BMJ"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1002\/cncr.32815","article-title":"Familial risk of breast cancer by dynamic, accumulative, and static definitions of family history","volume":"126","author":"Mukama","year":"2020","journal-title":"Cancer"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1002\/cncr.32815","article-title":"Familial risk of breast cancer by dynamic, accumulative, and static definitions of family history","volume":"126","author":"Mukama","year":"2020","journal-title":"Cancer"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13053-019-0114-8","article-title":"Examining intrafamilial communication of colorectal cancer risk status to family members and kin responses to colonoscopy: a qualitative study","volume":"17","author":"McGarragle","year":"2019","journal-title":"Hered Cancer Clin Pract"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ejca.2005.09.023","article-title":"Relative and absolute risk of colorectal cancer for individuals with a family history: a meta-analysis","volume":"42","author":"Butterworth","year":"2006","journal-title":"Eur J Cancer"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"980","DOI":"10.14309\/ajg.0000000000000639","article-title":"Increased risk of colorectal cancer tied to advanced colorectal polyps: an untapped opportunity to screen first-degree relatives and decrease cancer burden","volume":"115","author":"Kolb","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"836","DOI":"10.7326\/0003-4819-119-8-199310150-00010","article-title":"Polyp guideline: diagnosis, treatment, and surveillance for patients with nonfamilial colorectal polyps. The Practice Parameters Committee of the American College of Gastroenterology","volume":"119","author":"Bond","year":"1993","journal-title":"Ann Intern Med"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"12891","DOI":"10.1038\/srep12891","article-title":"Population landscape of familial cancer","volume":"5","author":"Frank","year":"2015","journal-title":"Sci Rep"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1053\/j.gastro.2016.01.015","article-title":"Family history of colorectal adenomas: taking the methodological bull by the horns","volume":"150","author":"Kahi","year":"2016","journal-title":"Gastroenterology"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1136\/gutjnl-2019-319511","article-title":"Global patterns and trends in colorectal cancer incidence in young adults","volume":"68","author":"Siegel","year":"2019","journal-title":"Gut"},{"key":"ref241","first-page":"41","article-title":"Invasive carcinomas may arise in colorectal adenomas with high-grade dysplasia and with carcinoma in situ","volume":"3","author":"Rubio","year":"2010","journal-title":"Int J Clin Exp Med"},{"key":"ref441","first-page":"865","article-title":"Familial risks in in situ cancers from the Family-Cancer Database","volume":"7","author":"Hemminki","year":"1998","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13053-019-0114-8","article-title":"Examining intrafamilial communication of colorectal cancer risk status to family members and kin responses to colonoscopy: a qualitative study","volume":"17","author":"McGarragle","year":"2019","journal-title":"Hered Cancer Clin Pract"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1053\/j.gastro.2018.08.017","article-title":"Clinical practice guideline on screening for colorectal cancer in individuals with a family history of nonhereditary colorectal cancer or adenoma: the Canadian Association of Gastroenterology Banff Consensus","volume":"155","author":"Leddin","year":"2018","journal-title":"Gastroenterology"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"ref501","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1053\/j.gastro.2018.08.017","article-title":"Clinical practice guideline on screening for colorectal cancer in individuals with a family history of nonhereditary colorectal cancer or adenoma: the Canadian Association of Gastroenterology Banff Consensus","volume":"155","author":"Leddin","year":"2018","journal-title":"Gastroenterology"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"e8076","DOI":"10.1136\/bmj.e8076","article-title":"Familial risk of early and late onset cancer: nationwide prospective cohort study","volume":"345","author":"Kharazmi","year":"2012","journal-title":"BMJ"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"djw322","DOI":"10.1093\/jnci\/djw322","article-title":"Colorectal cancer incidence patterns in the United States, 1974\u20132013","volume":"109","author":"Siegel","year":"2017","journal-title":"J Natl Cancer Inst"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1053\/j.gastro.2020.03.063","article-title":"Calculating starting age for screening in relatives of patients with colorectal cancer based on data from large nationwide datasets","volume":"159","author":"Tian","year":"2020","journal-title":"Gastroenterology"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.gie.2020.01.014","article-title":"Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer","volume":"91","author":"Gupta","year":"2020","journal-title":"Gastrointest Endosc"},{"key":"ref291","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-40618-3","volume-title":"AJCC Cancer Staging Manual","author":"Amin","year":"2017"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"l803","DOI":"10.1136\/bmj.l803","article-title":"Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study","volume":"364","author":"Tian","year":"2019","journal-title":"BMJ"}],"container-title":["Journal of the National Comprehensive Cancer Network"],"original-title":[],"link":[{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/19\/11\/article-p1252.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/19\/11\/article-p1252.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T21:47:11Z","timestamp":1699566431000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/19\/11\/article-p1252.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":50,"journal-issue":{"issue":"11"},"URL":"https:\/\/doi.org\/10.6004\/jnccn.2021.7004","relation":{},"ISSN":["1540-1405","1540-1413"],"issn-type":[{"value":"1540-1405","type":"print"},{"value":"1540-1413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11]]}}}