Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Early-onset colorectal cancer as an emerging disease of metabolic dysregulation

Nature Reviews Endocrinology volume 21, pages 686–702 (2025)Cite this article

Subjects

Abstract

Colorectal cancer (CRC) is one of the most common malignancies and the second leading cause of cancer-related death worldwide. Early-onset CRC (EOCRC), diagnosed in adults under the age of 50 years, has emerged as a pressing public health concern owing to its alarming rise in incidence since the 1990s. This trend, observed in the USA and at least eight other high-income countries, starkly contrasts with the declining incidence rates of late-onset CRC (age 50 years and above), largely attributed to early disease detection and lifestyle changes. Concurrent with the rising number of cases of EOCRC, the burden of metabolic diseases, particularly obesity and type 2 diabetes mellitus (T2DM), has surged among young populations. Despite well-documented links between metabolic dysfunction and late-onset CRC, understanding the precise role of obesity and T2DM in the pathogenesis of EOCRC remains in its infancy. This narrative Review synthesizes evidence on the relationship of obesity and T2DM with EOCRC, focusing on pathophysiological mechanisms and the mediating roles of diet and lifestyle factors. It also discusses potential clinical and public health strategies to address obesity and T2DM for EOCRC prevention, highlighting knowledge gaps and future research directions.

Key points

  • The incidence of early-onset colorectal cancer (EOCRC) is increasing globally, particularly in high-income countries, aligning with rising obesity and type 2 diabetes mellitus (T2DM) rates among young adults.

  • Obesity and T2DM could contribute to EOCRC through insulin resistance and/or hyperinsulinaemia, chronic inflammation and altered gut microbiome, which create a pro-tumorigenic environment that accelerates colorectal carcinogenesis.

  • Western diets high in ultra-processed foods, refined sugars and saturated fats exacerbate obesity, T2DM and EOCRC risk by disrupting insulin signalling, promoting chronic inflammation and altering the gut microbiome.

  • Current colorectal cancer screening guidelines might miss young adults at high risk; integrating metabolic factors, microbiome biomarkers and lifestyle data could improve individual risk assessments for EOCRC.

  • Tailored dietary programmes, physical activity, glucagon-like peptide 1 receptor agonists and metformin show potential for reducing EOCRC risk, although long-term efficacy and mechanisms require further study.

  • Multi-omics profiling, mechanistic studies and randomized controlled trials focusing on age-specific metabolic pathways, microbial signatures and socioenvironmental factors are essential for targeted EOCRC prevention.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Trends in the prevalence of obesity and diabetes mellitus and the incidence rate of colorectal cancer among people younger than 50 years in the USA from 1976 to 2018.
Fig. 2: Schematic representation of potential mechanisms linking obesity and T2DM to early-onset colorectal cancer.
Fig. 3: Directed acyclic graphs for hypothesized pathways to EOCRC and late-onset CRC.
Fig. 4: Clinical and public health approaches for the prevention of EOCRC.

Similar content being viewed by others

References

  1. World Health Organization. Colorectal Cancer https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer (2023).

  2. Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).

    PubMed  Google Scholar 

  3. Siegel, R. L. et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut 68, 2179–2185 (2019).

    PubMed  Google Scholar 

  4. Keum, N. & Giovannucci, E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat. Rev. Gastroenterol. Hepatol. 16, 713–732 (2019).

    PubMed  Google Scholar 

  5. Araghi, M. et al. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. Lancet Gastroenterol. Hepatol. 4, 511–518 (2019).

    PubMed  PubMed Central  Google Scholar 

  6. American Cancer Society. Colorectal Cancer Facts & Figures 2023-2025 (ACS, 2023).

  7. Sung, H. et al. Colorectal cancer incidence trends in younger versus older adults: an analysis of population-based cancer registry data. Lancet Oncol. 26, 51–63 (2025).

    PubMed  PubMed Central  Google Scholar 

  8. Blum‐Barnett, E. et al. Financial burden and quality of life among early‐onset colorectal cancer survivors: a qualitative analysis. Health Expect. 22, 1050–1057 (2019).

    PubMed  PubMed Central  Google Scholar 

  9. Khoo, A. M. et al. Understanding the psychosocial impact of colorectal cancer on young‐onset patients: a scoping review. Cancer Med. 11, 1688–1700 (2022).

    PubMed  PubMed Central  Google Scholar 

  10. Jasperson, K. W., Tuohy, T. M., Neklason, D. W. & Burt, R. W. Hereditary and familial colon cancer. Gastroenterology 138, 2044–2058 (2010).

    CAS  PubMed  Google Scholar 

  11. Sinicrope, F. A. Increasing incidence of early-onset colorectal cancer. N. Engl. J. Med. 386, 1547–1558 (2022).

    CAS  PubMed  Google Scholar 

  12. Cercek, A. et al. A comprehensive comparison of early-onset and average-onset colorectal cancers. J. Natl Cancer Inst. 113, 1683–1692 (2021).

    PubMed  PubMed Central  Google Scholar 

  13. Guinney, J. et al. The consensus molecular subtypes of colorectal cancer. Nat. Med. 21, 1350–1356 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  15. Siegel, R. L., Wagle, N. S., Cercek, A., Smith, R. A. & Jemal, A. Colorectal cancer statistics, 2023. CA Cancer J. Clin. 73, 233–254 (2023).

    PubMed  Google Scholar 

  16. Siegel, R. L., Kratzer, T. B., Giaquinto, A. N., Sung, H. & Jemal, A. Cancer statistics, 2025. CA Cancer J. Clin. 75, 10–45 (2025).

    PubMed  PubMed Central  Google Scholar 

  17. Siegel, R. L. et al. Colorectal cancer incidence patterns in the United States, 1974–2013. J. Natl Cancer Inst. 109, djw322 (2017).

    PubMed  PubMed Central  Google Scholar 

  18. Siegel, R. L., Medhanie, G. A., Fedewa, S. A. & Jemal, A. State variation in early-onset colorectal cancer in the United States, 1995–2015. J. Natl Cancer Inst. 111, 1104–1106 (2019).

    PubMed  PubMed Central  Google Scholar 

  19. Lieu, C. H. et al. Comprehensive genomic landscapes in early and later onset colorectal cancer. Clin. Cancer Res. 25, 5852–5858 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lawler, T., Parlato, L. & Warren Andersen, S. The histological and molecular characteristics of early-onset colorectal cancer: a systematic review and meta-analysis. Front. Oncol. 14, 1349572 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ogden, C. L. & Carroll, M. D. Prevalence of Overweight, Obesity, and Extreme Obesity Among Adults: United States, Trends 1960-62 Through 2007-2008 (NCHS, 2010).

  22. Fox, C. S. et al. Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s. Circulation 113, 2914–2918 (2006).

    PubMed  Google Scholar 

  23. Ellison-Barnes, A., Johnson, S. & Gudzune, K. Trends in obesity prevalence among adults aged 18 through 25 years, 1976-2018. JAMA 326, 2073–2074 (2021).

    PubMed  PubMed Central  Google Scholar 

  24. Flegal, K., Carroll, M., Kuczmarski, R. & Johnson, C. Overweight and obesity in the United States: prevalence and trends, 1960–1994. Int. J. Obes. 22, 39–47 (1998).

    CAS  Google Scholar 

  25. Li, M., Gong, W., Wang, S. & Li, Z. Trends in body mass index, overweight and obesity among adults in the USA, the NHANES from 2003 to 2018: a repeat cross-sectional survey. BMJ Open 12, e065425 (2021).

    Google Scholar 

  26. Nielsen, J., Narayan, K. V. & Cunningham, S. A. Incidence of obesity across adulthood in the United States, 2001–2017 — a national prospective analysis. Am. J. Clin. Nutr. 117, 141–148 (2023).

    PubMed  PubMed Central  Google Scholar 

  27. Rubino, F. et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 13, 221–262 (2025).

    PubMed  Google Scholar 

  28. Schulze, M. B. & Stefan, N. Metabolically healthy obesity: from epidemiology and mechanisms to clinical implications. Nat. Rev. Endocrinol. 20, 633–646 (2024).

    PubMed  Google Scholar 

  29. Romero-Corral, A. et al. Accuracy of body mass index to diagnose obesity in the US adult population. Int. J. Obes. 32, 959–966 (2008).

    CAS  Google Scholar 

  30. World Health Organization. Obesity and overweight. WHO https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (2024).

  31. Geiss, L. S. et al. Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980-2012. JAMA 312, 1218–1226 (2014).

    CAS  PubMed  Google Scholar 

  32. National Institute of Diabetes and Digestive and Kidney Diseases. Overweight & obesity statistics. niddk.nih.gov https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity (2021).

  33. Wagenknecht, L. E. et al. Trends in incidence of youth-onset type 1 and type 2 diabetes in the USA, 2002–18: results from the population-based SEARCH for Diabetes in Youth study. Lancet Diabetes Endocrinol. 11, 242–250 (2023).

    PubMed  PubMed Central  Google Scholar 

  34. Lawrence, J. M. et al. Trends in prevalence of type 1 and type 2 diabetes in children and adolescents in the US, 2001-2017. JAMA 326, 717–727 (2021).

    PubMed  PubMed Central  Google Scholar 

  35. Dong, W. et al. Geographic variation and risk factor association of early versus late onset colorectal cancer. Cancers 15, 1006 (2023).

    PubMed  PubMed Central  Google Scholar 

  36. Lauby-Secretan, B. et al. Body fatness and cancer-viewpoint of the IARC working group. N. Engl. J. Med. 375, 794–798 (2016).

    PubMed  PubMed Central  Google Scholar 

  37. Li, H., Boakye, D., Chen, X., Hoffmeister, M. & Brenner, H. Association of body mass index with risk of early-onset colorectal cancer: systematic review and meta-analysis. Am. J. Gastroenterol. 116, 2173–2183 (2021).

    PubMed  PubMed Central  Google Scholar 

  38. Liu, P.-H. et al. Association of obesity with risk of early-onset colorectal cancer among women. JAMA Oncol. 5, 37 (2018).

    PubMed Central  Google Scholar 

  39. Elangovan, A. et al. Colorectal cancer, age, and obesity-related comorbidities: a large database study. Dig. Dis. Sci. 66, 3156–3163 (2021).

    PubMed  Google Scholar 

  40. Caan, B. J. et al. Body size and the risk of colon cancer in a large case-control study. Int. J. Obes. Relat. Metab. Disord. 22, 178–184 (1998).

    CAS  PubMed  Google Scholar 

  41. Murphy, N. et al. Body mass index and molecular subtypes of colorectal cancer. J. Natl Cancer Inst. 115, 165–173 (2023).

    CAS  PubMed  Google Scholar 

  42. Hou, L. et al. Body mass index and colon cancer risk in Chinese people: menopause as an effect modifier. Eur. J. Cancer 42, 84–90 (2006).

    PubMed  PubMed Central  Google Scholar 

  43. Murphy, N. et al. Heterogeneity of colorectal cancer risk factors by anatomical subsite in 10 European countries: a multinational cohort study. Clin. Gastroenterol. Hepatol. 17, 1323–1331.e6 (2019).

    PubMed  PubMed Central  Google Scholar 

  44. Harlid, S. et al. Diabetes mellitus in relation to colorectal tumor molecular subtypes: a pooled analysis of more than 9000 cases. Int. J. Cancer 151, 348–360 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Li, Z. et al. Type 2 diabetes and risk of early-onset colorectal cancer. Gastro. Hep. Adv. 1, 186–193 (2022).

    PubMed  PubMed Central  Google Scholar 

  46. Ali Khan, U. et al. Personal history of diabetes as important as family history of colorectal cancer for risk of colorectal cancer: a nationwide cohort study. Am. J. Gastroenterol. 115, 1103–1109 (2020).

    PubMed  Google Scholar 

  47. Archambault, A. N. et al. Nongenetic determinants of risk for early-onset colorectal cancer. JNCI Cancer Spectr. 5, pkab029 (2021).

    PubMed  PubMed Central  Google Scholar 

  48. Luo, C. et al. Associations between blood glucose and early- and late-onset colorectal cancer: evidence from two prospective cohorts and Mendelian randomization analyses. J. Natl Cancer Cent. 4, 241–248 (2024).

    PubMed  PubMed Central  Google Scholar 

  49. Ma, Y. et al. Obesity and risk of colorectal cancer: a systematic review of prospective studies. PLoS ONE 8, e53916 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Guraya, S. Y. Association of type 2 diabetes mellitus and the risk of colorectal cancer: a meta-analysis and systematic review. World J. Gastroenterol. 21, 6026–6031 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Hopkins, B. D., Goncalves, M. D. & Cantley, L. C. Insulin–PI3K signalling: an evolutionarily insulated metabolic driver of cancer. Nat. Rev. Endocrinol. 16, 276–283 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Pollak, M. Insulin and insulin-like growth factor signalling in neoplasia. Nat. Rev. Cancer 8, 915–928 (2008).

    CAS  PubMed  Google Scholar 

  53. Sridhar, S. S. & Goodwin, P. J. Insulin-insulin-like growth factor axis and colon cancer. J. Clin. Oncol. 27, 165–167 (2009).

    PubMed  Google Scholar 

  54. Kahn, S. E., Hull, R. L. & Utzschneider, K. M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840–846 (2006).

    CAS  PubMed  Google Scholar 

  55. Fruman, D. A. et al. The PI3K pathway in human disease. Cell 170, 605–635 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Ryu, T. Y., Park, J. & Scherer, P. E. Hyperglycemia as a risk factor for cancer progression. Diabetes Metab. J. 38, 330–336 (2014).

    PubMed  PubMed Central  Google Scholar 

  57. Lahm, H. et al. Blockade of the insulin-like growth-factor-I receptor inhibits growth of human colorectal cancer cells: evidence of a functional IGF-II-mediated autocrine loop. Int. J. Cancer 58, 452–459 (1994).

    CAS  PubMed  Google Scholar 

  58. Giovannucci, E. et al. A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol. Biomark. Prev. 9, 345–349 (2000).

    CAS  Google Scholar 

  59. Ma, J. et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J. Natl Cancer Inst. 91, 620–625 (1999).

    CAS  PubMed  Google Scholar 

  60. Sancar, G. & Birkenfeld, A. L. The role of adipose tissue dysfunction in hepatic insulin resistance and T2D. J. Endocrinol. 262, e240115 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Rohm, T. V., Meier, D. T., Olefsky, J. M. & Donath, M. Y. Inflammation in obesity, diabetes, and related disorders. Immunity 55, 31–55 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Sanchez-Garrido, M. A. & Tena-Sempere, M. Metabolic dysfunction in polycystic ovary syndrome: pathogenic role of androgen excess and potential therapeutic strategies. Mol. Metab. 35, 100937 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Martins, L. M. et al. Type B insulin resistance syndrome: a systematic review. Arch. Endocrinol. Metab. 64, 337–348 (2020).

    PubMed  PubMed Central  Google Scholar 

  64. Ouchi, N., Parker, J. L., Lugus, J. J. & Walsh, K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11, 85–97 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Donath, M. Y., Dinarello, C. A. & Mandrup-Poulsen, T. Targeting innate immune mediators in type 1 and type 2 diabetes. Nat. Rev. Immunol. 19, 734–746 (2019).

    CAS  PubMed  Google Scholar 

  66. Schmitt, M. & Greten, F. R. The inflammatory pathogenesis of colorectal cancer. Nat. Rev. Immunol. 21, 653–667 (2021).

    CAS  PubMed  Google Scholar 

  67. Canli, Ö. et al. Myeloid cell-derived reactive oxygen species induce epithelial mutagenesis. Cancer Cell 32, 869–883.e5 (2017).

    CAS  PubMed  Google Scholar 

  68. Janney, A., Powrie, F. & Mann, E. H. Host-microbiota maladaptation in colorectal cancer. Nature 585, 509–517 (2020).

    CAS  PubMed  Google Scholar 

  69. Schmitt, M. et al. Paneth cells respond to inflammation and contribute to tissue regeneration by acquiring stem-like features through SCF/c-kit signaling. Cell Rep. 24, 2312–2328.e7 (2018).

    CAS  PubMed  Google Scholar 

  70. Pesic, M. & Greten, F. R. Inflammation and cancer: tissue regeneration gone awry. Curr. Opin. Cell Biol. 43, 55–61 (2016).

    CAS  PubMed  Google Scholar 

  71. Nenci, A. et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446, 557–561 (2007).

    CAS  PubMed  Google Scholar 

  72. Shaked, H. et al. Chronic epithelial NF-κB activation accelerates APC loss and intestinal tumor initiation through iNOS up-regulation. Proc. Natl Acad. Sci. USA 109, 14007–14012 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Visser, M., Bouter, L. M., McQuillan, G. M., Wener, M. H. & Harris, T. B. Elevated C-reactive protein levels in overweight and obese adults. JAMA 282, 2131–2135 (1999).

    CAS  PubMed  Google Scholar 

  74. Esposito, K. et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289, 1799–1804 (2003).

    CAS  PubMed  Google Scholar 

  75. Samaras, K., Botelho, N. K., Chisholm, D. J. & Lord, R. V. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity 18, 884–889 (2010).

    CAS  PubMed  Google Scholar 

  76. Keum, N., Lee, D. H., Kim, R., Greenwood, D. C. & Giovannucci, E. L. Visceral adiposity and colorectal adenomas: dose-response meta-analysis of observational studies. Ann. Oncol. 26, 1101–1109 (2015).

    CAS  PubMed  Google Scholar 

  77. Ahechu, P. et al. NLRP3 inflammasome: a possible link between obesity-associated low-grade chronic inflammation and colorectal cancer development. Front. Immunol. 9, 2918 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. González, P., Lozano, P., Ros, G. & Solano, F. Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. Int. J. Mol. Sci. 24, 9352 (2023).

    PubMed  PubMed Central  Google Scholar 

  79. Cani, P. D. Microbiota and metabolites in metabolic diseases. Nat. Rev. Endocrinol. 15, 69–70 (2019).

    CAS  PubMed  Google Scholar 

  80. Piccinno, G. et al. Pooled analysis of 3,741 stool metagenomes from 18 cohorts for cross-stage and strain-level reproducible microbial biomarkers of colorectal cancer. Nat. Med. 31, 2416–2429 (2025).

    PubMed  PubMed Central  Google Scholar 

  81. Garrett, W. S. The gut microbiota and colon cancer. Science 364, 1133–1135 (2019).

    CAS  PubMed  Google Scholar 

  82. Sánchez-Alcoholado, L. et al. Gut microbiota-mediated inflammation and gut permeability in patients with obesity and colorectal cancer. Int. J. Mol. Sci. 21, 6782 (2020).

    PubMed  PubMed Central  Google Scholar 

  83. Casarin, R. C. V. et al. Subgingival biodiversity in subjects with uncontrolled type-2 diabetes and chronic periodontitis. J. Periodontal Res. 48, 30–36 (2013).

    CAS  PubMed  Google Scholar 

  84. Rubinstein, M. R. et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 14, 195–206 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Kasai, C. et al. Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: terminal restriction fragment length polymorphism and next-generation sequencing analyses. Oncol. Rep. 35, 325–333 (2016).

    CAS  PubMed  Google Scholar 

  86. Viljoen, K. S., Dakshinamurthy, A., Goldberg, P. & Blackburn, J. M. Quantitative profiling of colorectal cancer-associated bacteria reveals associations between Fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer. PLoS ONE 10, e0119462 (2015).

    PubMed  PubMed Central  Google Scholar 

  87. Gurung, M. et al. Role of gut microbiota in type 2 diabetes pathophysiology. eBioMedicine 51, 102590 (2020).

    PubMed  PubMed Central  Google Scholar 

  88. Kostic, A. D., Chun, E., Meyerson, M. & Garrett, W. S. Microbes and inflammation in colorectal cancer. Cancer Immunol. Res. 1, 150–157 (2013).

    CAS  PubMed  Google Scholar 

  89. Gur, C. et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42, 344–355 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Ma, W. et al. Dietary fiber intake, the gut microbiome, and chronic systemic inflammation in a cohort of adult men. Genome Med. 13, 102 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Piperni, E. et al. Intestinal Blastocystis is linked to healthier diets and more favorable cardiometabolic outcomes in 56,989 individuals from 32 countries. Cell 187, 4554–4570.e18 (2024).

    CAS  PubMed  Google Scholar 

  92. Rooks, M. G. & Garrett, W. S. Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol. 16, 341–352 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Vinolo, M. A. R. et al. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J. Nutr. Biochem. 22, 849–855 (2011).

    CAS  PubMed  Google Scholar 

  94. Chang, P. V., Hao, L., Offermanns, S. & Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl Acad. Sci. USA 111, 2247–2252 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Tao, R. et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat. Med. 13, 1299–1307 (2007).

    CAS  PubMed  Google Scholar 

  96. Wu, S.-E. et al. Microbiota-derived metabolite promotes HDAC3 activity in the gut. Nature 586, 108–112 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Nguyen, T. T. et al. Lithocholic acid stimulates IL-8 expression in human colorectal cancer cells via activation of Erk1/2 MAPK and suppression of STAT3 activity. J. Cell Biochem. 118, 2958–2967 (2017).

    CAS  PubMed  Google Scholar 

  98. Cadena Sandoval, M. & Haeusler, R. A. Bile acid metabolism in type 2 diabetes mellitus. Nat. Rev. Endocrinol. 21, 203–213 (2025).

    CAS  PubMed  Google Scholar 

  99. Ahmad, T. R. & Haeusler, R. A. Bile acids in glucose metabolism and insulin signalling — mechanisms and research needs. Nat. Rev. Endocrinol. 15, 701–712 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Jia, W., Xie, G. & Jia, W. Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat. Rev. Gastroenterol. Hepatol. 15, 111–128 (2018).

    CAS  PubMed  Google Scholar 

  101. Van Hul, M. & Cani, P. D. The gut microbiota in obesity and weight management: microbes as friends or foe? Nat. Rev. Endocrinol. 19, 258–271 (2023).

    PubMed  Google Scholar 

  102. Koh, A. et al. Microbially produced imidazole propionate impairs insulin signaling through mTORC1. Cell 175, 947–961.e17 (2018).

    CAS  PubMed  Google Scholar 

  103. Yang, Y. et al. Dysbiosis of human gut microbiome in young-onset colorectal cancer. Nat. Commun. 12, 6757 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Díaz-Gay, M. et al. Geographic and age variations in mutational processes in colorectal cancer. Nature 643, 230–240 (2025).

    PubMed  PubMed Central  Google Scholar 

  105. Harb, A. A., Shechter, A., Koch, P. A. & St-Onge, M.-P. Ultra-processed foods and the development of obesity in adults. Eur. J. Clin. Nutr. 77, 619–627 (2023).

    PubMed  Google Scholar 

  106. Jannasch, F., Kröger, J. & Schulze, M. B. Dietary patterns and type 2 diabetes: a systematic literature review and meta-analysis of prospective studies12. J. Nutr. 147, 1174–1182 (2017).

    CAS  PubMed  Google Scholar 

  107. Wang, Y. et al. Association between the sulfur microbial diet and risk of colorectal cancer. JAMA Netw. Open 4, e2134308 (2021).

    PubMed  PubMed Central  Google Scholar 

  108. Carbonero, F., Benefiel, A. C., Alizadeh-Ghamsari, A. H. & Gaskins, H. R. Microbial pathways in colonic sulfur metabolism and links with health and disease. Front. Physiol. 3, 448 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Zheng, X. et al. Comprehensive assessment of diet quality and risk of precursors of early-onset colorectal cancer. J. Natl Cancer Inst. 113, 543–552 (2021).

    PubMed  Google Scholar 

  110. Carroll, K. L., Frugé, A. D., Heslin, M. J., Lipke, E. A. & Greene, M. W. Diet as a risk factor for early-onset colorectal adenoma and carcinoma: a systematic review. Front. Nutr. 9, 896330 (2022).

    PubMed  PubMed Central  Google Scholar 

  111. Cani, P. D. et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 1470–1481 (2008).

    CAS  PubMed  Google Scholar 

  112. Song, H. et al. High-fat diet plus HNF1A variant promotes polyps by activating β-catenin in early-onset colorectal cancer. JCI Insight 8, e167163 (2023).

    PubMed  PubMed Central  Google Scholar 

  113. Whelan, K., Bancil, A. S., Lindsay, J. O. & Chassaing, B. Ultra-processed foods and food additives in gut health and disease. Nat. Rev. Gastroenterol. Hepatol. 21, 406–427 (2024).

    PubMed  Google Scholar 

  114. Monteiro, C. A. et al. Ultra-processed foods: what they are and how to identify them. Public Health Nutr. 22, 936–941 (2019).

    PubMed  PubMed Central  Google Scholar 

  115. Juul, F., Parekh, N., Martinez-Steele, E., Monteiro, C. A. & Chang, V. W. Ultra-processed food consumption among US adults from 2001 to 2018. Am. J. Clin. Nutr. 115, 211–221 (2022).

    CAS  PubMed  Google Scholar 

  116. Rauber, F. et al. Ultra-processed foods and excessive free sugar intake in the UK: a nationally representative cross-sectional study. BMJ Open 9, e027546 (2019).

    PubMed  PubMed Central  Google Scholar 

  117. Hall, K. D. et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of Ad libitum food intake. Cell Metab. 30, 67–77.e3 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Poti, J. M., Braga, B. & Qin, B. Ultra-processed food intake and obesity: what really matters for health — processing or nutrient content? Curr. Obes. Rep. 6, 420–431 (2017).

    PubMed  PubMed Central  Google Scholar 

  119. Delpino, F. M. et al. Ultra-processed food and risk of type 2 diabetes: a systematic review and meta-analysis of longitudinal studies. Int. J. Epidemiol. 51, 1120–1141 (2022).

    PubMed  Google Scholar 

  120. Du, M. et al. Ultraprocessed food intake and body mass index change among youths: a prospective cohort study. Am. J. Clin. Nutr. 120, 836–845 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Wang, Y. et al. Maternal consumption of ultra-processed foods and subsequent risk of offspring overweight or obesity: results from three prospective cohort studies. BMJ 379, e071767 (2022).

    PubMed  PubMed Central  Google Scholar 

  122. Wang, C. et al. 178: ultra-processed food consumption and risk of early-onset colorectal cancer precursors among women: a prospective US cohort study. Gastroenterology 169, S-46 (2025).

    Google Scholar 

  123. Wang, L. et al. Association of ultra-processed food consumption with colorectal cancer risk among men and women: results from three prospective US cohort studies. BMJ 378, e068921 (2022).

    PubMed  PubMed Central  Google Scholar 

  124. Hur, J. et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut 70, 2330–2336 (2021).

    CAS  PubMed  Google Scholar 

  125. Todoric, J. et al. Fructose stimulated de novo lipogenesis is promoted by inflammation. Nat. Metab. 2, 1034–1045 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Spruss, A., Kanuri, G., Stahl, C., Bischoff, S. C. & Bergheim, I. Metformin protects against the development of fructose-induced steatosis in mice: role of the intestinal barrier function. Lab. Invest. 92, 1020–1032 (2012).

    CAS  PubMed  Google Scholar 

  127. Jin, R. et al. Fructose induced endotoxemia in pediatric nonalcoholic fatty liver disease. Int. J. Hepatol. 2014, 560620 (2014).

    PubMed  PubMed Central  Google Scholar 

  128. Lambertz, J., Weiskirchen, S., Landert, S. & Weiskirchen, R. Fructose: a dietary sugar in crosstalk with microbiota contributing to the development and progression of non-alcoholic liver disease. Front. Immunol. 8, 1159 (2017).

    PubMed  PubMed Central  Google Scholar 

  129. Goncalves, M. D. et al. High-fructose corn syrup enhances intestinal tumor growth in mice. Science 363, 1345–1349 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Meslier, V. et al. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut 69, 1258–1268 (2020).

    CAS  PubMed  Google Scholar 

  131. Qian, F., Liu, G., Hu, F. B., Bhupathiraju, S. N. & Sun, Q. Association between plant-based dietary patterns and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA Intern. Med. 179, 1335–1344 (2019).

    PubMed  PubMed Central  Google Scholar 

  132. Wang, P. et al. Optimal dietary patterns for prevention of chronic disease. Nat. Med. 29, 719–728 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Wang, L. et al. Risk factor profiles differ for cancers of different regions of the colorectum. Gastroenterology 159, 241–256.e13 (2020).

    PubMed  Google Scholar 

  134. Zhao, L. et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359, 1151–1156 (2018).

    CAS  PubMed  Google Scholar 

  135. Makki, K., Deehan, E. C., Walter, J. & Bäckhed, F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 23, 705–715 (2018).

    CAS  PubMed  Google Scholar 

  136. Lipkin, M., Reddy, B., Newmark, H. & Lamprecht, S. A. Dietary factors in human colorectal cancer. Annu. Rev. Nutr. 19, 545–586 (1999).

    CAS  PubMed  Google Scholar 

  137. Seethaler, B. et al. Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial. Am. J. Clin. Nutr. 116, 928–942 (2022).

    PubMed  Google Scholar 

  138. Wang, D. D. et al. The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk. Nat. Med. 27, 333–343 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Shan, Z. et al. Trends in dietary carbohydrate, protein, and fat intake and diet quality among US adults, 1999-2016. JAMA 322, 1178–1187 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Lin, B.-H. & Guthrie, J. Over time, racial and ethnic gaps in dietary fiber consumption per 1,000 calories have widened. Economic Research Service. US Department of Agriculture https://www.ers.usda.gov/data-products/charts-of-note/chart-detail?chartId=106189 (2023).

  141. Aleksandrova, K. et al. Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort. Int. J. Epidemiol. 46, 1823–1835 (2017).

    PubMed  Google Scholar 

  142. Nguyen, L. H. et al. Sedentary behaviors, TV viewing time, and risk of young-onset colorectal cancer. JNCI Cancer Spectr. 2, pky073 (2018).

    PubMed  Google Scholar 

  143. Jin, E. H. et al. Sex and tumor-site differences in the association of alcohol intake with the risk of early-onset colorectal cancer. J. Clin. Oncol. 41, 3816–3825 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Siler, S. Q., Neese, R. A. & Hellerstein, M. K. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am. J. Clin. Nutr. 70, 928–936 (1999).

    CAS  PubMed  Google Scholar 

  145. Syed-Abdul, M. M. et al. The tailgate study: differing metabolic effects of a bout of excessive eating and drinking. Alcohol 90, 45–55 (2021).

    CAS  PubMed  Google Scholar 

  146. Suter, P. M., Schutz, Y. & Jequier, E. The effect of ethanol on fat storage in healthy subjects. N. Engl. J. Med. 326, 983–987 (1992).

    CAS  PubMed  Google Scholar 

  147. Cao, Y. et al. Long-term use of antibiotics and risk of colorectal adenoma. Gut 67, 672–678 (2018).

    CAS  PubMed  Google Scholar 

  148. Zhang, J. et al. Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: a matched case-control study. Gut 68, 1971–1978 (2019).

    CAS  PubMed  Google Scholar 

  149. Nguyen, L. H. et al. Antibiotic therapy and risk of early-onset colorectal cancer: a national case-control study. Clin. Transl. Gastroenterol. 13, e00437 (2022).

    PubMed  PubMed Central  Google Scholar 

  150. Kane, K. J. et al. Oral antibiotic use in adulthood and risk of early-onset colorectal cancer: a case-control study. Clin. Gastroenterol. Hepatol. 23, 1440–1447.e5 (2025).

    CAS  PubMed  Google Scholar 

  151. US Preventive Services Task Force. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA 325, 1965–1977 (2021).

    Google Scholar 

  152. Wolf, A. M. D. et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J. Clin. 68, 250–281 (2018).

    PubMed  Google Scholar 

  153. Rex, D. K. et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am. J. Gastroenterol. 112, 1016–1030 (2017).

    PubMed  Google Scholar 

  154. Wang, K. et al. Endoscopic screening and risk of colorectal cancer according to type 2 diabetes status. Cancer Prev. Res. 15, 847–856 (2022).

    Google Scholar 

  155. Jeon, J. et al. Determining risk of colorectal cancer and starting age of screening based on lifestyle, environmental, and genetic factors. Gastroenterology 154, 2152–2164.e19 (2018).

    PubMed  Google Scholar 

  156. Liang, J. Q. et al. Fecal microbial DNA markers serve for screening colorectal neoplasm in asymptomatic subjects. J. Gastroenterol. Hepatol. 36, 1035–1043 (2021).

    CAS  PubMed  Google Scholar 

  157. Liang, J. Q. et al. A novel faecal Lachnoclostridium marker for the non-invasive diagnosis of colorectal adenoma and cancer. Gut 69, 1248–1257 (2020).

    CAS  PubMed  Google Scholar 

  158. Jensen, M. D. et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society. J. Am. Coll. Cardiol. 63, 2985–3023 (2014).

    PubMed  Google Scholar 

  159. Webb, V. L. & Wadden, T. A. Intensive lifestyle intervention for obesity: principles, practices, and results. Gastroenterology 152, 1752–1764 (2017).

    PubMed  Google Scholar 

  160. Ali, M. K., Echouffo-Tcheugui, J. & Williamson, D. F. How effective were lifestyle interventions in real-world settings that were modeled on the diabetes prevention program? Health Aff. 31, 67–75 (2012).

    Google Scholar 

  161. Rock, C. L. et al. Effect of a free prepared meal and incentivized weight loss program on weight loss and weight loss maintenance in obese and overweight women: a randomized controlled trial. JAMA 304, 1803–1810 (2010).

    CAS  PubMed  Google Scholar 

  162. Jebb, S. A. et al. Primary care referral to a commercial provider for weight loss treatment versus standard care: a randomised controlled trial. Lancet 378, 1485–1492 (2011).

    PubMed  PubMed Central  Google Scholar 

  163. Jolly, K. et al. Comparison of range of commercial or primary care led weight reduction programmes with minimal intervention control for weight loss in obesity: lighten up randomised controlled trial. BMJ 343, d6500 (2011).

    PubMed  PubMed Central  Google Scholar 

  164. Rock, C. L., Pakiz, B., Flatt, S. W. & Quintana, E. L. Randomized trial of a multifaceted commercial weight loss program. Obesity 15, 939–949 (2007).

    PubMed  Google Scholar 

  165. Berry, S. E. et al. Human postprandial responses to food and potential for precision nutrition. Nat. Med. 26, 964–973 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Wyatt, P. et al. Postprandial glycaemic dips predict appetite and energy intake in healthy individuals. Nat. Metab. 3, 523–529 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Asnicar, F. et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat. Med. 27, 321–332 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Bermingham, K. M. et al. Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial. Nat. Med. 30, 1888–1897 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  169. Wang, L., Wang, W., Kaelber, D. C., Xu, R. & Berger, N. A. GLP-1 receptor agonists and colorectal cancer risk in drug-naive patients with type 2 diabetes, with and without overweight/obesity. JAMA Oncol. 10, 256–258 (2024).

    PubMed  Google Scholar 

  170. Higurashi, T. et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 17, 475–483 (2016).

    CAS  PubMed  Google Scholar 

  171. Zell, J. A. et al. A phase IIa trial of metformin for colorectal cancer risk reduction among individuals with history of colorectal adenomas and elevated body mass index. Cancer Prev. Res. 13, 203–212 (2020).

    CAS  Google Scholar 

  172. Salpeter, S. R., Buckley, N. S., Kahn, J. A. & Salpeter, E. E. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am. J. Med. 121, 149–157.e2 (2008).

    CAS  PubMed  Google Scholar 

  173. Jastreboff, A. M. et al. Tirzepatide once weekly for the treatment of obesity. N. Engl. J. Med. 387, 205–216 (2022).

    CAS  PubMed  Google Scholar 

  174. Drew, D. A. & Chan, A. T. Aspirin in the prevention of colorectal neoplasia. Annu. Rev. Med. 72, 415–430 (2021).

    CAS  PubMed  Google Scholar 

  175. Low, E. E. et al. Risk factors for early-onset colorectal cancer. Gastroenterology 159, 492–501.e7 (2020).

    CAS  PubMed  Google Scholar 

  176. Malik, V. S. & Hu, F. B. The role of sugar-sweetened beverages in the global epidemics of obesity and chronic diseases. Nat. Rev. Endocrinol. 18, 205–218 (2022).

    PubMed  PubMed Central  Google Scholar 

  177. Du, M. et al. Cost-effectiveness of a national sugar-sweetened beverage tax to reduce cancer burdens and disparities in the United States. JNCI Cancer Spectr. 4, pkaa073 (2020).

    PubMed  PubMed Central  Google Scholar 

  178. Andreyeva, T., Marple, K., Marinello, S., Moore, T. E. & Powell, L. M. Outcomes following taxation of sugar-sweetened beverages: a systematic review and meta-analysis. JAMA Netw. Open 5, e2215276 (2022).

    PubMed  PubMed Central  Google Scholar 

  179. Teng, A. M. et al. Impact of sugar-sweetened beverage taxes on purchases and dietary intake: systematic review and meta-analysis. Obes. Rev. 20, 1187–1204 (2019).

    PubMed  PubMed Central  Google Scholar 

  180. U.S. Food and Drugs Administration. FDA issues proposed rule on front-of-package nutrition labeling. FDA https://www.fda.gov/food/hfp-constituent-updates/fda-issues-proposed-rule-front-package-nutrition-labeling (2025).

  181. Shangguan, S. et al. A meta-analysis of food labeling effects on consumer diet behaviors and industry practices. Am. J. Prev. Med. 56, 300–314 (2019).

    PubMed  Google Scholar 

  182. Ding, M., Bhupathiraju, S. N., Chen, M., van Dam, R. M. & Hu, F. B. Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis. Diabetes Care 37, 569–586 (2014).

    PubMed  PubMed Central  Google Scholar 

  183. Liu, B. et al. Chocolate intake and risk of type 2 diabetes: prospective cohort studies. BMJ 387, e078386 (2024).

    PubMed  PubMed Central  Google Scholar 

  184. Tabrizi, R. et al. The effects of caffeine intake on weight loss: a systematic review and dos-response meta-analysis of randomized controlled trials. Crit. Rev. Food Sci. Nutr. 59, 2688–2696 (2019).

    CAS  PubMed  Google Scholar 

  185. Mozaffarian, D., Hao, T., Rimm, E. B., Willett, W. C. & Hu, F. B. Changes in diet and lifestyle and long-term weight gain in women and men. N. Engl. J. Med. 364, 2392–2404 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Sayon-Orea, C., Martínez-González, M. A., Ruiz-Canela, M. & Bes-Rastrollo, M. Associations between yogurt consumption and weight gain and risk of obesity and metabolic syndrome: a systematic review. Adv. Nutr. 8, 146S–154S (2017).

    PubMed  PubMed Central  Google Scholar 

  187. Eales, J. et al. Is consuming yoghurt associated with weight management outcomes? Results from a systematic review. Int. J. Obes. 40, 731–746 (2016).

    CAS  Google Scholar 

  188. Alvarez-Bueno, C. et al. Effects of milk and dairy product consumption on type 2 diabetes: overview of systematic reviews and meta-analyses. Adv. Nutr. 10, S154–S163 (2019).

    PubMed  PubMed Central  Google Scholar 

  189. Ugai, S. et al. Long-term yogurt intake and colorectal cancer incidence subclassified by Bifidobacterium abundance in tumor. Gut Microbes 17, 2452237 (2025).

    PubMed  PubMed Central  Google Scholar 

  190. Um, C. Y. et al. Coffee consumption and risk of colorectal cancer in the Cancer Prevention Study-II nutrition cohort. Cancer Epidemiol. 67, 101730 (2020).

    PubMed  Google Scholar 

  191. Schmit, S. L., Rennert, H. S., Rennert, G. & Gruber, S. B. Coffee consumption and the risk of colorectal cancer. Cancer Epidemiol. Biomark. Prev. 25, 634–639 (2016).

    CAS  Google Scholar 

  192. AlZaabi, A., Younus, H. A., Al-Reasi, H. A. & Al-Hajri, R. Could environmental exposure and climate change be a key factor in the rising incidence of early onset colorectal cancer? Heliyon 10, e35935 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  193. Kim, J. Y. et al. Different risk factors for advanced colorectal neoplasm in young adults. World J. Gastroenterol. 22, 3611–3620 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Kantor, E. D. et al. Adolescent body mass index and erythrocyte sedimentation rate in relation to colorectal cancer risk. Gut 65, 1289–1295 (2016).

    CAS  PubMed  Google Scholar 

  195. Levi, Z. et al. Adolescent body mass index and risk of colon and rectal cancer in a cohort of 1.79 million Israeli men and women: a population-based study. Cancer 123, 4022–4030 (2017).

    PubMed  Google Scholar 

  196. Dash, C. et al. Obesity is an initiator of colon adenomas but not a promoter of colorectal cancer in the Black Women’s Health Study. Cancer Causes Control. 31, 291–302 (2020).

    PubMed  PubMed Central  Google Scholar 

  197. Jin, E. H. et al. Association between metabolic syndrome and the risk of colorectal cancer diagnosed before age 50 years according to tumor location. Gastroenterology 163, 637–648.e2 (2022).

    PubMed  Google Scholar 

  198. Yue, Y. et al. Prospective evaluation of dietary and lifestyle pattern indices with risk of colorectal cancer in a cohort of younger women. Ann. Oncol. 32, 778–786 (2021).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge support to the PROSPECT team of the Cancer Grand Challenges partnership funded by Cancer Research UK (CGCATF-2023/100037 to Y.C.; CGCATF-2023/100036 to A.T.C.), the National Cancer Institute (OT2CA297576 to Y.C.; OT2CA297680 to A.T.C.), the Bowelbabe Fund for Cancer Research UK and Institut National Du Cancer. The support of this work by R35CA253185 (A.T.C.), R37CA246175 (Y.C.), R01CA258697 (M.D.G.), and K00CA274714 and K99CA297022 (M.D.) from the National Cancer Institute; R01DK132427 (M.D.G.) and K01DK120742 (D.A.D.) from the National Institute of Diabetes and Digestive and Kidney Diseases are also acknowledged.

Author information

Authors and Affiliations

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

    Mengxi Du

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

    Mengxi Du

  3. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Mengxi Du, David A. Drew & Andrew T. Chan

  4. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    David A. Drew & Andrew T. Chan

  5. New York University Langone Health, New York, NY, USA

    Marcus D. Goncalves

  6. Department of Medicine at New York University Grossman School of Medicine, New York, NY, USA

    Marcus D. Goncalves

  7. Department of Radiation Oncology at New York University Grossman School of Medicine, New York, NY, USA

    Marcus D. Goncalves

  8. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Yin Cao

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

    Yin Cao

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

    Yin Cao

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

    Andrew T. Chan

  12. Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Andrew T. Chan

  13. Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Andrew T. Chan

Authors
  1. Mengxi Du
    View author publications

    Search author on:PubMed Google Scholar

  2. David A. Drew
    View author publications

    Search author on:PubMed Google Scholar

  3. Marcus D. Goncalves
    View author publications

    Search author on:PubMed Google Scholar

  4. Yin Cao
    View author publications

    Search author on:PubMed Google Scholar

  5. Andrew T. Chan
    View author publications

    Search author on:PubMed Google Scholar

Contributions

M.D. researched data for the article and wrote the article. M.D. and A.T.C. contributed substantially to discussion of the content. All authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Andrew T. Chan.

Ethics declarations

Competing interests

M.D.G. holds equity in Faeth Therapeutics and Skye Biosciences; reports consulting or advisory roles with Almac Discovery, Genentech Inc., Faeth Therapeutics, Scorpion Therapeutics and Skye Biosciences; and patents, royalties and other intellectual property with Weill Cornell Medicine and Faeth Therapeutics. Y.C. has served as a consultant for Need Inc. and Geneocopy Inc. A.T.C. serves as a consultant for Pfizer Inc. and Boehringer Ingelheim. All of the above disclosures are outside of the submitted work. The other authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Endocrinology thanks Michael Greene, Lorne Hofseth and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Du, M., Drew, D.A., Goncalves, M.D. et al. Early-onset colorectal cancer as an emerging disease of metabolic dysregulation. Nat Rev Endocrinol 21, 686–702 (2025). https://doi.org/10.1038/s41574-025-01159-z

Download citation

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41574-025-01159-z

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer