Importance of Family History of Colorectal Carcinoma In Situ Versus Invasive Colorectal Cancer: A Nationwide Cohort Study

Authors: Yu Tian PhD1,2,3, Elham Kharazmi MD, PhD1,4,5, Hermann Brenner MD, PhD1,6,7, Xing Xu PhD1,2, Kristina Sundquist MD, PhD4,8,9, Jan Sundquist MD, PhD4,8,9, and Mahdi Fallah MD, PhD1,4,10
View More View Less
  • 1 Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), and
  • | 2 Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany;
  • | 3 School of Public Health, Capital Medical University, Beijing, China;
  • | 4 Center for Primary Health Care Research, Lund University, Malmö, Sweden;
  • | 5 Statistical Genetics Group, Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, Germany;
  • | 6 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany;
  • | 7 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany;
  • | 8 Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York;
  • | 9 Center for Community-based Healthcare Research and Education, Department of Functional Pathology, School of Medicine, Shimane University, Japan; and
  • | 10 Department of Global Public Health and Primary Care, Faculty of Medicine, University of Bergen, Norway.

Background: 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. Patients and Methods: 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. Results: The lifetime (0–79 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5–1.7; 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, 1.6–1.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1–3.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3–2.1; 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. Conclusions: 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.

Submitted July 24, 2020; final revision received November 29, 2020; accepted for publication January 7, 2021. Published online September 13, 2021.

Author contributions: Study concept: Kharazmi, Fallah. Data curation: Kharazmi, Fallah. Formal analysis: Tian, Kharazmi, Fallah. Funding acquisition: Tian, Fallah. Investigation: Kharazmi. Methodology: Tian, Kharazmi, Fallah. Project administration: Kharazmi, Fallah. Resources: K. Sundquist, J. Sundquist. Software: Tian, Kharazmi, Xu. Supervision: Kharazmi, Fallah. Validation: Kharazmi, Fallah. Writing–original draft: Tian. Writing–review and editing: All authors.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Xing Xu has received support from the China Scholarship Council.

Disclaimer: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Correspondence: Mahdi Fallah, MD, PhD, Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. Email: m.fallah@dkfz.de

Supplementary Materials

    • Supplemental Materials (PDF 546 KB)
  • 1.

    Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209249.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Amin MB, Edge S, Greene F, et al., eds. AJCC Cancer Staging Manual, 8th ed. New York, NY: Springer International Publishing; 2017.

  • 3.

    National Cancer Institute. Stage 0 colorectal carcinoma in situ. Accessed May 29, 2020. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/stage-0-colorectal-carcinoma-in-situ

    • Search Google Scholar
    • Export Citation
  • 4.

    Fleming M, Ravula S, Tatishchev SF, et al. Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol 2012;3:153173.

  • 5.

    Butterworth AS, Higgins JP, Pharoah P. Relative and absolute risk of colorectal cancer for individuals with a family history: a meta-analysis. Eur J Cancer 2006;42:216227.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Tian Y, Kharazmi E, Sundquist K, et al. Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study. BMJ 2019;364:l803.

  • 7.

    Tian Y, Kharazmi E, Brenner H, et al. Calculating starting age for screening in relatives of patients with colorectal cancer based on data from large nationwide datasets. Gastroenterology 2020;159:159168.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Siegel RL, Fedewa SA, Anderson WF, et al. Colorectal cancer incidence patterns in the United States, 1974–2013. J Natl Cancer Inst 2017;109:djw322.

  • 9.

    Siegel RL, Torre LA, Soerjomataram I, et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut 2019;68:21792185.

  • 10.

    Kharazmi E, Fallah M, Sundquist K, et al. Familial risk of early and late onset cancer: nationwide prospective cohort study. BMJ 2012;345:e8076.

  • 11.

    Hemminki K, Ji J, Brandt A, et al. The Swedish Family-Cancer Database 2009: prospects for histology-specific and immigrant studies. Int J Cancer 2010;126:22592267.

    • Search Google Scholar
    • Export Citation
  • 12.

    Barlow L, Westergren K, Holmberg L, et al. The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol 2009;48:2733.

  • 13.

    Mukama T, Kharazmi E, Sundquist K, et al. Familial risk of breast cancer by dynamic, accumulative, and static definitions of family history. Cancer 2020;126:28372848.

  • 14.

    Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with nonfamilial colorectal polyps. The Practice Parameters Committee of the American College of Gastroenterology. Ann Intern Med 1993;119:836843.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    World Health Organization. World health statistics 2016: monitoring health for the SDGs, sustainable development goals. Accessed May 29, 2020. Available at: http://www.who.int/iris/handle/10665/206498

    • Search Google Scholar
    • Export Citation
  • 16.

    Frank C, Fallah M, Sundquist J, et al. Population landscape of familial cancer. Sci Rep 2015;5:12891.

  • 17.

    Hemminki K, Vaittinen P. Familial risks in in situ cancers from the Family-Cancer Database. Cancer Epidemiol Biomarkers Prev 1998;7:865868.

  • 18.

    Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2020;91:463485.e5.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    National Colorectal Cancer Roundtable. Advanced Colorectal Polyp Brief. Accessed September 30, 2020. Available at: https://nccrt.org/resource/advanced-colorectal-polyp-brief/

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Molmenti CL, Kolb JM, Karlitz JJ. Advanced colorectal polyps on colonoscopy: a trigger for earlier screening of family members. Am J Gastroenterol 2020;115:311314.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Kolb JM, Molmenti CL, Patel SG, et al. Increased risk of colorectal cancer tied to advanced colorectal polyps: an untapped opportunity to screen first-degree relatives and decrease cancer burden. Am J Gastroenterol 2020;115:980988.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Rex DK, Boland CR, Dominitz JA, et al. colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2017;112:10161030.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Leddin D, Lieberman DA, Tse F, et al. 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. Gastroenterology 2018;155:13251347.e3.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Kahi CJ, Lieberman D. Family history of colorectal adenomas: taking the methodological bull by the horns. Gastroenterology 2016;150:550552.

  • 25.

    Rubio CA, Delinassios JG. Invasive carcinomas may arise in colorectal adenomas with high-grade dysplasia and with carcinoma in situ. Int J Clin Exp Med 2010;3:4147.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Armaghany T, Wilson JD, Chu Q, et al. Genetic alterations in colorectal cancer. Gastrointest Cancer Res 2012;5:1927.

  • 27.

    McGarragle KM, Hare C, Holter S, et al. Examining intrafamilial communication of colorectal cancer risk status to family members and kin responses to colonoscopy: a qualitative study. Hered Cancer Clin Pract 2019;17:16.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Terry MB, Neugut AI, Bostick RM, et al. Reliability in the classification of advanced colorectal adenomas. Cancer Epidemiol Biomarkers Prev 2002;11:660663.

    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 350 350 350
PDF Downloads 179 179 179
EPUB Downloads 0 0 0