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Gut instinct: a call to study the biology of early-onset colorectal cancer disparities

Nature Reviews Cancer volume 21, pages 339–340 (2021)Cite this article

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Colorectal cancer (CRC) incidence among individuals age younger than 50 years continues to rise with etiologies unknown. Synchronously, early-onset CRC disparities have grown more pronounced. As translational research across diverse populations has been limited, we advocate for mechanistic studies that address this challenge to mitigate CRC disparities among young adults.

Despite reductions in the overall colorectal cancer (CRC) burden, the incidence of CRC among individuals younger than age 50 (early-onset CRC; EOCRC) has increased over the past two decades worldwide. Long-term projections suggest that by 2030, approximately one in ten colon cancer and one in four rectal cancer diagnoses in the US will be EOCRC1. Yet across diverse populations, the CRC — and EOCRC — burden sharply varies. By sex, CRC incidence rates are nearly one-third higher among men, but women have a higher incidence of right-sided colon cancers. Among patients with EOCRC, men harbor a 12–18% increased hazard of disease-specific death versus women2. The proportion of individuals with EOCRC is also nearly twofold higher among people of colour versus white people. The disproportionate burden of CRCs in young African Americans (AAs) may reflect larger shares of this adult population that are <37 years of age. However, as clinical features of EOCRC differ across racial or ethnic groups, and survival after disease diagnosis is significantly worse among AAs versus white people, these data point to unique molecular underpinnings of EOCRC.

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Fig. 1: Multi-level factors and domains contributing to early-onset CRC disparities.

References

  1. Bailey, C. E. et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg. 150, 17–22 (2015).

    Article  Google Scholar 

  2. Holowatyj, A. N. et al. Racial/ethnic disparities in survival among patients with young-onset colorectal cancer. J. Clin. Oncol. 34, 2148–2156 (2016).

    Article  Google Scholar 

  3. Holowatyj, A. N. et al. Distinct molecular phenotype of sporadic colorectal cancers among young patients based on multiomics analysis. Gastroenterology 158, 1155–1158 (2020).

    Article  CAS  Google Scholar 

  4. Devall, M. et al. Racial disparities in epigenetic aging of the right vs left colon. J. Natl Cancer Inst. https://doi.org/10.1093/jnci/djaa207 (2020).

    Article  PubMed  Google Scholar 

  5. Paredes, J. et al. Immune-related gene expression and cytokine secretion is reduced among African American colon cancer patients. Front. Oncol. 10, 1498 (2020).

    Article  Google Scholar 

  6. Willauer, A. N. et al. Clinical and molecular characterization of early-onset colorectal cancer. Cancer 125, 2002–2010 (2019).

    Article  CAS  Google Scholar 

  7. Saunders, B. P. et al. Why is colonoscopy more difficult in women? Gastrointest. Endosc. 43, 124–126 (1996).

    Article  CAS  Google Scholar 

  8. Cai, Y. et al. Sex differences in colon cancer metabolism reveal a novel subphenotype. Sci. Rep. 10, 4905 (2020).

    Article  CAS  Google Scholar 

  9. Zhao, L. et al. Effect of chronic psychological stress on liver metastasis of colon cancer in mice. PLoS ONE 10, e0139978 (2015).

    Article  Google Scholar 

  10. Yan, H. H. N. et al. Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles. Gut 69, 2165–2179 (2020).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

A.N.H. was supported by the National Institutes of Health (NIH) K12 HD043483 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. This work was also supported by the American Cancer Society (#IRG-19-139-59) to A.N.H., and NIH/National Cancer Institute R01CA229259 to C.H.L.

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Authors and Affiliations

  1. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Andreana N. Holowatyj

  2. Vanderbilt-Ingram Cancer Center, Nashville, TN, USA

    Andreana N. Holowatyj

  3. Fundación Jiménez Díaz University Hospital, Madrid, Spain

    Jose Perea

  4. University of Colorado Denver, Aurora, CO, USA

    Christopher H. Lieu

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  1. Andreana N. Holowatyj
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  2. Jose Perea
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  3. Christopher H. Lieu
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Correspondence to Andreana N. Holowatyj.

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Holowatyj, A.N., Perea, J. & Lieu, C.H. Gut instinct: a call to study the biology of early-onset colorectal cancer disparities. Nat Rev Cancer 21, 339–340 (2021). https://doi.org/10.1038/s41568-021-00356-y

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