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Rising incidence of early-onset colorectal cancer — a call to action

Nature Reviews Clinical Oncology volume 18, pages 230–243 (2021)Cite this article

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Abstract

The incidence of early-onset colorectal cancer (CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity. Early-onset CRCs have differential clinical, pathological and molecular features compared with later-onset CRCs. Certain existing resources can be utilized to elucidate the aetiology of early-onset CRC and inform the development of effective prevention, early detection and therapeutic strategies; however, additional life-course cohort studies spanning childhood and young adulthood, integrated with prospective biospecimen collections, omics biomarker analyses and a molecular pathological epidemiology approach, are needed to better understand and manage this disease entity. In this Perspective, we summarize our current understanding of early-onset CRC and discuss how we should strategize future research to improve its prevention and clinical management.

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Fig. 1: Examples of life-course exposures with potential effects on CRC tumorigenesis.

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Acknowledgements

The authors thank Tyler Twombly (Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Boston, USA) for proofreading of the manuscript. The work of the authors is supported by US NIH grants (R35 CA197735 and R01 CA248857 to S.O., R21 CA230873 to S.O. and K.W., R01 CA205406 to K.N., R03 CA197879 to K.W., and R37 CA246175 to Y.C.), a Cancer Research UK Grand Challenge Award (UK C10674/A27140 to M.G., K.N. and S.O.), an Investigator Initiated Grant from the American Institute for Cancer Research (AICR) to K.W., and by a US Department of Defense grant (CA160344 to K.N.). K.N. and M.G. have received support from the Project P Fund. The work of M.G. has been supported by a Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant (SU2C-AACR-DT22-17) administered by the American Association for Cancer Research, a scientific partner of SU2C. The work of T.U. has been supported by an Overseas Research Fellowship grant (201960541) from the Japan Society for the Promotion of Science, the Uehara Memorial Foundation and the Yasuda Medical Foundation. The work of K.F. has been supported by fellowship grants from the Uehara Memorial Foundation and the Grant of The Clinical Research Promotion Foundation (2018). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Author notes

  1. These authors contributed equally: Naohiko Akimoto, Tomotaka Ugai, Rong Zhong

  2. These authors jointly supervised this work: Yin Cao, Kimmie Ng and Shuji Ogino

Authors and Affiliations

  1. Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Naohiko Akimoto, Tomotaka Ugai, Rong Zhong, Kenji Fujiyoshi & Shuji Ogino

  2. Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan

    Naohiko Akimoto

  3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Tomotaka Ugai, Kana Wu & Shuji Ogino

  4. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Rong Zhong & Kana Wu

  5. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China

    Rong Zhong

  6. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Tsuyoshi Hamada

  7. Department of Surgery, Kurume University, Kurume, Japan

    Kenji Fujiyoshi

  8. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Marios Giannakis & Kimmie Ng

  9. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Marios Giannakis & Shuji Ogino

  10. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Marios Giannakis

  11. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Kana Wu

  12. Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA

    Yin Cao

  13. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Yin Cao

  14. Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Yin Cao

  15. Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA

    Shuji Ogino

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  1. Naohiko Akimoto
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Contributions

All of the authors contributed to the conceptualization of the article and approved the final version of the manuscript. S.O. developed the initial basic concept and supervised the manuscript preparation. N.A., T.U., R.Z., K.F. and S.O. constructed the overall outline of the manuscript, searched the literature and drafted the manuscript. T.H., M.G., K.W., Y.C., K.N. and S.O. revised the manuscript critically for important intellectual content.

Corresponding author

Correspondence to Shuji Ogino.

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Competing interests

K.N. has received institutional research funding from Evergrande Group, Genentech, Gilead Sciences, Pharmavite, Revolution Medicines, Tarrex Biopharma and Trovagene, and has served on advisory boards for Array Biopharma, Bayer and Seattle Genetics. M.G. has received research funding from Bristol-Myers Squibb and Merck. The other authors declare no competing interests.

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Nature Reviews Clinical Oncology thanks Samir Gupta, Jose Perea and Benjamin Weinberg for their contribution to the peer review of this work.

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Related links

Child Health and Development Studies (CHDS): http://www.chdstudies.org/

Colon Cancer Family Registry (CCFR) Cohort: https://www.coloncfr.org/

Growing Up in New Zealand: https://www.growingup.co.nz/

Growing Up Today Study 2 (GUTS2): https://nhs2survey.org/gutswordpress/index.php/about/history/

Millennium Cohort Study: https://cls.ucl.ac.uk/cls-studies/millennium-cohort-study/

National Children’s Study: https://www.nichd.nih.gov/research/supported/NCS

Nurses’ Health Study 3 (NHS3): https://www.nhs3.org/

ORIGINS Project: https://originsproject.telethonkids.org.au/

SEER Cancer Statistics Review 1975–2017: https://seer.cancer.gov/csr/1975_2017/

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Akimoto, N., Ugai, T., Zhong, R. et al. Rising incidence of early-onset colorectal cancer — a call to action. Nat Rev Clin Oncol 18, 230–243 (2021). https://doi.org/10.1038/s41571-020-00445-1

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